The EMMY longitudinal, cohort study: real-world data to describe multiple myeloma management and outcomes as more therapeutic options emerge.

The therapeutic management of patients with multiple myeloma (MM) is complex. Despite substantial advances, MM remains incurable, and management involves cycles of treatment response, disease relapse, and further therapy. Currently, evidence to support the therapeutic decision is limited. Thus, the EMMY longitudinal, real-world study was designed to annually assess therapeutic management of MM in France to provide evidence to support physicians. During an annual prespecified 3-month recruitment period, eligible patients will be identified from their medical records. Adults aged ≥18 years diagnosed with symptomatic MM and requiring systemic treatment will be eligible. The primary objective, the evolution of MM therapeutic management, will be described, as well as the impact on the following outcomes: time-to-next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). The study plans to recruit 5000 patients over 6 years: 700 to 900 patients annually. EMMY is a unique opportunity to collect real-world data to describe the evolving MM therapeutic landscape and record outcomes in France. These data will provide annual snapshots of various aspects of MM management. This knowledge will provide physicians with real-life, evidence-based data for therapeutic decision-making and ultimately improve treatment for MM patients.

Colic incidence, risk factors, and therapeutic management in a working horse population in Tuban, Indonesia.

Background and Aim: Colic is the primary problem affecting equestrian care worldwide. The primary cause of colic is digestive diseases; however, they can also affect organs from different systems in the abdominal region. In addition to a prior history of the disease and its treatment, risk factors may be assessed to determine the etiology of the disease in horses without or with a history of colic. This study aimed to present a summary of the incidence, risk factors, and medical procedures for colic in horses. Materials and Methods: Based on owner reports, 223 horses in Tuban, Indonesia, suspected of having colic were investigated. During the investigation of clinical parameters, investigators went door-to-door with interested horse owners to gather information about potential risk factors related to equine colic. Information on horses diagnosed with colic was obtained from the medical records of treatment. A Chi-square test was used to investigate the potential association between the risk factors, medical protocol, and the outcome of colic in horses. Results: Of the 187 cases, spasmodic colic was the most common (48.13%), but 17 (9.09%) had no definitive diagnosis. Poor body condition scores (χ2 = 58.73; p < 0.001), wheat bran feeding (χ2 = 26.79; p < 0.001), concentrate (χ2 = 10.66; p < 0.01), less access to water (χ2 = 128.24; p < 0.001), recurrence of colic (χ2 = 85.64; p < 0.001), no deworming program (χ2 = 54.76; p < 0.001), the presence of gastrointestinal parasites (χ2 = 56.79; p < 0.001), stressed physical activity (χ2 = 28.53; p < 0.001), and summer season (χ2 = 7.83; p < 0.01) were the risk factors for colic. We further reported that 185 (98.93%) patients who received the following medical interventions recovered: injection of non-steroidal anti-inflammatory drugs was necessary, Vitamin B complex (χ2 = 39.98; p < 0.001), fluid therapy (χ2 = 92.99; p < 0.001), and gastric intubation (χ2 = 4.09; p < 0.05). Conclusion: The importance of colic was demonstrated in 187 (83.86%) of the 223 horses investigated in Tuban, Indonesia, documented. In this study, recommendations for medical procedures when colic risk factors have been determined are presented.

Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma.

BACKGROUND: Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. AIM: To provide an updated overview of risk factors, prognosis, and management of CSRCC. METHODS: A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. RESULTS: In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CONCLUSION: CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.

A review on mechanistic insights into structure and function of dystrophin protein in pathophysiology and therapeutic targeting of Duchenne muscular dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive and severe muscle weakening and degeneration. Among the various forms of muscular dystrophy, it stands out as one of the most common and impactful, predominantly affecting boys. The condition arises due to mutations in the dystrophin gene, a key player in maintaining the structure and function of muscle fibers. The manuscript explores the structural features of dystrophin protein and their pivotal roles in DMD. We present an in-depth analysis of promising therapeutic approaches targeting dystrophin and their implications for the therapeutic management of DMD. Several therapies aiming to restore dystrophin protein or address secondary pathology have obtained regulatory approval, and many others are ongoing clinical development. Notably, recent advancements in genetic approaches have demonstrated the potential to restore partially functional dystrophin forms. The review also provides a comprehensive overview of the status of clinical trials for major therapeutic genetic approaches for DMD. In addition, we have summarized the ongoing therapeutic approaches and advanced mechanisms of action for dystrophin restoration and the challenges associated with DMD therapeutics.

Cranial Neuropathy As Initial Manifestation of Primary Sjögren's Syndrome: A Case Series With Literature Review.

The clinical spectrum of primary Sjögren's syndrome (PSS) extends beyond its classical manifestations. This work explores an unusual aspect of PSS, namely the initial presentation of cranial neuropathy. The study was conducted over a period of 22 months, from January 2022 to October 2023. Of 58 PSS patients, only five (four women and one man) had cranial neuropathy as their initial manifestation. Only one patient had sixth cranial nerve involvement, three had acute optic neuritis (second cranial nerve), and three had fifth cranial nerve involvement. The diagnosis of PSS was retained according to the 2016 ACR-EULAR criteria. All patients received symptomatic and immunosuppressive treatments. The course was favorable for all patients. The purpose of this case series is to show that cranial neuropathy can be the initial manifestation of PSS, which should be systematically investigated after the elimination of the most common etiologies of cranial neuropathy, particularly in the elderly.

Link between circadian rhythm and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS).

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging males, affecting 50% of men over 50 and up to 80% of men over 80 years old. Its negative impact on health-related quality of life implores further investigation into its risk factors and strategies for effective management. Although the exact molecular mechanisms underlying pathophysiological onset of BPH are poorly defined, the current hypothesized contributors to BPH and lower urinary tract symptoms (LUTS) include aging, inflammation, metabolic syndrome, and hormonal changes. These processes are indirectly influenced by circadian rhythm disruption. In this article, we review the recent evidence on the potential association of light changes/circadian rhythm disruption and the onset of BPH and impact on treatment. METHODS: A narrative literature review was conducted using PubMed and Google Scholar to identify supporting evidence. The articles referenced ranged from 1975 to 2023. RESULTS: A clear relationship between BPH/LUTS and circadian rhythm disruption is yet to be established. However, common mediators influence both diseases, including proinflammatory states, metabolic syndrome, and hormonal regulation that can be asserted to circadian disruption. Some studies have identified a possible relationship between general LUTS and sleep disturbance, but little research has been done on the medical management of these diseases and how circadian rhythm disruption further affects treatment outcomes. CONCLUSIONS: There is evidence to implicate a relationship between BPH/LUTS and circadian rhythm disruptions. However, there is scarce literature on potential specific link in medical management of the disease and treatment outcomes with circadian rhythm disruption. Further study is warranted to provide BPH patients with insights into circadian rhythm directed appropriate interventions.

Claudin-18.2 testing and its impact in the therapeutic management of patients with gastric and gastroesophageal adenocarcinomas: A literature review with expert opinion.

Claudin-18.2 (CLDN18.2) is a member of the tight junction protein family and is a highly selective biomarker with frequent abnormal expression during the occurrence and development of various primary malignant tumors, including gastric cancer (GC) and esophago-gastric junction adenocarcinomas (EGJA). For these reasons, CLDN18.2 has been investigated as a therapeutic target for GC/EGJA malignancies. Recently, zolbetuximab has been proposed as a new standard of care for patients with CLDN18.2-positive, HER2-negative, locally advanced and metastatic GC/EGJA. The use of CLDN18 IHC assays to select patients who might benefit from anti-CLDN18.2 therapy is currently entering clinical practice. In this setting, pathologists play a central role in therapeutic decision-making. Accurate biomarker assessment is essential to ensure the best therapeutic option for patients. In the present review, we provide a comprehensive overview of available evidence on CLDN18.2 testing and its impact on the therapeutic management of patients with GC/EGJA, as well as some practical suggestions for CLDN18.2 staining interpretation and potential pitfalls in the real-world setting.

Pulmonary tuberculosis and diabetes mellitus: Epidemiology, pathogenesis and therapeutic management (Review).

The dual burden of pulmonary tuberculosis (PTB) and diabetes mellitus (DM) is a major global public health concern. There is increasing evidence to indicate an association between PTB and DM. DM is associated with immune dysfunction and altered immune components. Hyperglycemia weakens the innate immune response by affecting the function of macrophages, dendritic cells, neutrophils, and natural killer cells, and also disrupts the adaptive immune response, thus promoting the susceptibility of PTB in patients with DM. Antituberculosis drugs often cause the impairment of liver and kidney function in patients with PTB, and the infection with Mycobacterium tuberculosis weaken pancreatic endocrine function by causing islet cell amyloidosis, which disrupts glucose metabolism and thus increases the risk of developing DM in patients with PTB. The present review discusses the association between PTB and DM from the perspective of epidemiology, pathogenesis, and treatment management. The present review aims to provide information for the rational formulation of treatment strategies for patients with PTB-DM.

Molecular and computational characterization of ABCB11 and ABCG5 variants in Tunisian patients with neonatal/infantile low-GGT intrahepatic cholestasis: Genetic diagnosis and genotype-phenotype correlation assessment.

Many inherited conditions cause hepatocellular cholestasis in infancy, including progressive familial intrahepatic cholestasis (PFIC), a heterogeneous group of diseases with highly overlapping symptoms. In our study, six unrelated Tunisian infants with PFIC suspicion were the subject of a panel-target sequencing followed by an exhaustive bioinformatic and modeling investigations. Results revealed five disease-causative variants including known ones: (the p.Asp482Gly and p.Tyr354 * in the ABCB11 gene and the p.Arg446 * in the ABCC2 gene), a novel p.Ala98Cys variant in the ATP-binding cassette subfamily G member 5 (ABCG5) gene and a first homozygous description of the p.Gln312His in the ABCB11 gene. The p.Gln312His disrupts the interaction pattern of the bile salt export pump as well as the flexibility of the second intracellular loop domain harboring this residue. As for the p.Ala98Cys, it modulates both the interactions within the first nucleotide-binding domain of the bile transporter and its accessibility. Two additional potentially modifier variants in cholestasis-associated genes were retained based on their pathogenicity (p.Gly758Val in the ABCC2 gene) and functionality (p.Asp19His in the ABCG8 gene). Molecular findings allowed a PFIC2 diagnosis in five patients and an unexpected diagnosis of sisterolemia in one case. The absence of genotype/phenotype correlation suggests the implication of environmental and epigenetic factors as well as modifier variants involved directly or indirectly in the bile composition, which could explain the cholestasis phenotypic variability.

Desmoid Tumors in the Active Surveillance Era: Evaluation of Treatment Options and Pain Relief in a Single-Center Retrospective Analysis.

In patients with desmoid tumors (DTs), active surveillance has been increasingly preferred over surgery, while treatment (including pharmacological therapy, radiotherapy, and/or surgery) is performed in cases with confirmed disease progression. This study aimed to evaluate event-free survival and pain management according to different treatment strategies. We evaluated event-free survival, including recurrence after initial surgical treatment or changes in the therapeutic management after initial non-surgical treatment and pain management according to different treatment strategies. All patients referred for DT in 2001-2021 at our institutions were stratified into four groups: those treated surgically prior to 2012 (SGPre12) or after 2012 (SGPost12), those treated pharmacologically (MG), and those under active surveillance (ASG). An event was defined as recurrence after initial surgical treatment or a change in therapeutic management. Overall, 123 patients were included in the study: 28 in SGPre12, 41 in SGPost12, 38 in MG, and 16 in ASG. Pharmacological treatment resolved painful symptoms in 16/27 (60%) patients (p = 0.0001). The median follow-up duration was 40 months (IQR 23-74). Event-free survival at 1, 3, and 5 years was: 85%, 70%, and 62% in SGPre12; 76%, 58%, and 49% in SGPost12; 49%, 31%, and 31% in MG; and 45%, 45%, and 45% in ASG. Our findings support the role of active surveillance as initial management, as demonstrated by the fact that about half the patients did not experience any progression, while surgery can be reserved as a first-line approach for selected patients. In terms of pain relief, medical therapy led to symptom resolution in more than half the cases.

Acute heart failure: mechanisms and pre-clinical models-a Scientific Statement of the ESC Working Group on Myocardial Function.

While chronic heart failure (CHF) treatment has considerably improved patient prognosis and survival, the therapeutic management of acute heart failure (AHF) has remained virtually unchanged in the last decades. This is partly due to the scarcity of pre-clinical models for the pathophysiological assessment and, consequently, the limited knowledge of molecular mechanisms involved in the different AHF phenotypes. This scientific statement outlines the different trajectories from acute to CHF originating from the interaction between aetiology, genetic and environmental factors, and comorbidities. Furthermore, we discuss the potential molecular targets capable of unveiling new therapeutic perspectives to improve the outcome of the acute phase and counteracting the evolution towards CHF.

Rehabilitation following extra-articular proximal phalangeal fractures of the fingers in adults: a scoping review.

Introduction: Proximal phalangeal fractures are common and can have a significant impact on hand function. Therefore, it is important to optimise post-operative rehabilitation. A scoping review was undertaken to map the existing evidence on rehabilitation of proximal phalangeal fractures of the fingers in adults. Methods: A comprehensive search was conducted which included database searching, reference searching, hand searching of journals, and searching for grey literature. Eight articles were included after screening for eligibility. Results: Three studies researched surgical interventions and five studies conservative management. The immobilisation period varied between 5 days to 3 weeks in the surgical studies, and between 3 to 7 weeks in the conservative studies. Active exercise therapy was started immediately with conservative management, while in the surgical studies time to commence exercises varied between 5 days and 3 weeks. All studies reported good results in mobility with a mean total active motion ranging from 240° to 258.9°. Patients reported little pain at final follow-up and grip strength recovered to 96% compared to the unaffected side. Studies reporting on function and patient satisfaction lacked transparency. Conclusions: All studies had a moderate to high risk of bias and the results of the included studies should therefore be interpreted with caution. More high-quality randomised controlled studies with an a priori research protocol and a standard set of outcome measures are necessary to research whether early motion, an intrinsic plus splint leaving the wrist free, and the inclusion of additional treatment modalities can result in a better and/or faster recovery.

Pulmonary fibrosis: from pathogenesis to clinical decision-making.

Pulmonary fibrosis (PF) encompasses a spectrum of chronic lung diseases that progressively impact the interstitium, resulting in compromised gas exchange, breathlessness, diminished quality of life (QoL), and ultimately respiratory failure and mortality. Various diseases can cause PF, with their underlying causes primarily affecting the lung interstitium, leading to their referral as interstitial lung diseases (ILDs). The current understanding is that PF arises from abnormal wound healing processes triggered by various factors specific to each disease, leading to excessive inflammation and fibrosis. While significant progress has been made in understanding the molecular mechanisms of PF, its pathogenesis remains elusive. This review provides an in-depth exploration of the latest insights into PF pathophysiology, diagnosis, treatment, and future perspectives.

Incidence, risk factors, and therapeutic management of equine colic in Lamongan, Indonesia.

Background and Aim: Colic is among the common health issues in equine health management. Gastrointestinal (GI) disorders are the most frequent causes of colic, but dysfunction of other organs and systems inside the abdominal cavity may also contribute. Therefore, it is crucial to identify risk factors for colic of specific etiologies. This study aimed to examine the incidence, risk factors, and best therapeutic management practices for horses with colic. Materials and Methods: A cohort of 256 horses living in Lamongan, East Java, Indonesia, was randomly recruited based on reports of colic symptoms by owners. Diagnosis and treatment were then conducted with the help of owners. Symptom profiles, risk factors, and therapeutic management strategies were analyzed by Chi-square tests. Results: Of 256 horses enrolled, 217 (84%) were diagnosed with colic, of which 172 (79.3%) were cases of spasmodic colic, 33 (15.2%) of impaction colic, and 12 (5.5%) of intestinal obstruction/displacement. Male sex (χ2 = 16.27; p < 0.001), wheat bran feeding (χ2 = 15.49; p < 0.001), concentrate feed intake >5 kg/day (χ2 = 24.95; p < 0.001), no regular anthelmintic drug treatment (χ2 = 67.24; p < 0.001), GI parasite infection (χ2 = 65.11; p < 0.001), recurrent colic (χ2 = 91.09; p < 0.001), poor body condition score (χ2 = 71.81; p < 0.001), limited daily water access (χ2 = 127.92; p < 0.001), and indications of dental disease (χ2 = 9.03; p < 0.001) were identified as risk factors. The most effective therapies were gastric intubation (χ2 = 153.54; p < 0.001), Vitamin B complex injection (χ2 = 32.09; p < 0.001), fluid therapy (χ2 = 42.59; p < 0.001), and non-steroidal anti-inflammatory drug injection (NSAID). Conclusion: Colic is highly prevalent among horses in Lamongan, East Java, Indonesia. Proper diet, workload management, regular access to clean drinking water, and dental care can reduce colic risk. Recommended therapies include NSAID injection without other analgesics or spasmolytics, fluid therapy, Vitamin B complex, and gastric intubation.

Catecholaminergic Polymorphic Ventricular Tachycardia: A Review of Therapeutic Strategies.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmia provoked by exercise or emotion. Most cases are caused by pathogenic variants in the gene encoding the cardiac ryanodine receptor (RYR2). The options for treating patients with CPVT have increased during the years, and evidence suggests that these have led to lower arrhythmic event rates. In addition, numerous potential new therapies are being investigated. In this review, we summarize the state of knowledge on both established and potential future treatment strategies for patients with CPVT and describe our approach to their management.

Deep Analysis of Clinical Parameters and Temporal Evolution of Glycemic Parameters Based on CGM Data for the Characterization of Severe Hypoglycemia in a Cohort of Children and Adolescents with Type 1 Diabetes.

This study aims to evaluate the determinants and clinical markers of patients at risk for severe hypoglycemia (SH) in children and adolescents with type 1 diabetes. In the EPI-GLUREDIA study, clinical parameters and continuous glucose monitoring metrics from children and adolescents with type 1 diabetes were retrospectively analyzed between July 2017 and June 2022. Their clinical parameters were collected during traditional and quarterly medical consultations according to whether they experienced severe hypoglycemia or not. Then, continuous glucose monitoring metrics were analyzed on days surrounding SH during specific periods. According to the glycemic parameters, glycemic hemoglobin and glycemic mean were significantly lower in the three months preceding a SH compared with during three normal months (p < 0.05). Moreover, the time spent in hypoglycemia(time below the range, TBR<3.3) and its strong correlation (R = 0.9, p < 0.001) with the frequency of SH represent a sensitive and specific clinical parameter to predict SH (cut-off: 9%, sensitivity: 71%, specificity: 63%). The second finding of the GLUREDIA study is that SH is not an isolated event in the glycemic follow-up of our T1DM patients. Indeed, most of the glycemic parameters (i.e., glycemic mean, glycemic variability, frequency of hypoglycemia, and glycemic targets) vary considerably in the month preceding an SH (all p < 0.05), whereas most of these studied glycemic parameters remain stable in the absence of a severe acute complication (all p > 0.05). Furthermore, the use of ROC curves allowed us to determine for each glycemic parameter a sensitive or specific threshold capable of more accurately predicting SH. For example, a 10% increase in the frequency of hypoglycemia predicts a risk of near SH with good combination of sensitivity and specificity (sensitivity: 80%, specificity: 60%). The GLUREDIA study aimed to target clinical and glycemic parameters to predict patients at risk for SH. First, we identified TBR<3.3 < 9% as a sensitive and specific tool to reduce the frequency of SH. In addition, SH was not an isolated event but rather it was accompanied by glycemic disturbances in the 30 days before SH.

Low-risk HPLLs/ABC score patients with splenic marginal zone lymphoma can be safely managed without treatment: Results from a prospective Spanish study.

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.

An international multicentre evaluation of treatment strategies for combined hepatocellular-cholangiocarcinoma✰.

Background & Aims: Management of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is not well-defined. Therefore, we evaluated the management of cHCC-CCA using an online hospital-wide multicentre survey sent to expert centres. Methods: A survey was sent to members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the International Cholangiocarcinoma Research Network (ICRN), in July 2021. To capture the respondents' contemporary decision-making process, a hypothetical case study with different tumour size and number combinations was embedded. Results: Of 155 surveys obtained, 87 (56%) were completed in full and included for analysis. Respondents represented Europe (68%), North America (20%), Asia (11%), and South America (1%) and included surgeons (46%), oncologists (29%), and hepatologists/gastroenterologists (25%). Two-thirds of the respondents included at least one new patient with cHCC-CCA per year. Liver resection was reported as the most likely treatment for a single cHCC-CCA lesion of 2.0-6.0 cm (range: 73-93%) and for two lesions, one up to 6 cm and a second well-defined lesion of 2.0 cm (range: 60-66%). Nonetheless, marked interdisciplinary differences were noted. Surgeons mainly adhered to resection if technically feasible, whereas up to half of the hepatologists/gastroenterologists and oncologists switched to alternative treatment options with increasing tumour burden. Fifty-one (59%) clinicians considered liver transplantation as an option for patients with cHCC-CCA, with the Milan criteria defining the upper limit of inclusion. Overall, well-defined cHCC-CCA treatment policies were lacking and management was most often dependent on local expertise. Conclusions: Liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Marked interdisciplinary differences were reported, depending on local expertise. These findings stress the need for a well-defined multicentre prospective trial comparing treatments, including liver transplantation, to optimise the therapeutic management of cHCC-CCA. Impact and implications: Because the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), a rare form of liver cancer, is currently not well-defined, we evaluated the contemporary treatment of this rare tumour type through an online survey sent to expert centres around the world. Based on the responses from 87 clinicians (46% surgeons, 29% oncologists, 25% hepatologists/gastroenterologists), representing four continents and 25 different countries, we found that liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Nonetheless, marked differences in treatment decisions were reported among the different specialties (surgeon vs. oncologist vs. hepatologist/gastroenterologist), highlighting the urgent need for a standardisation of therapeutic strategies for patients with cHCC-CCA.

Idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating lung disease with substantial morbidity. It is associated with cough, dyspnea and impaired quality of life. If left untreated, IPF has a median survival of 3 years. IPF affects âˆ¼3 million people worldwide, with increasing incidence in older patients. The current concept of pathogenesis is that pulmonary fibrosis results from repetitive injury to the lung epithelium, with fibroblast accumulation, myofibroblast activation, and deposition of matrix. These injuries, in combination with innate and adaptive immune responses, dysregulated wound repair and fibroblast dysfunction, lead to recurring tissue remodeling and self-perpetuating fibrosis as seen in IPF. The diagnostic approach includes the exclusion of other interstitial lung diseases or underlying conditions and depends on a multidisciplinary team-based discussion combining radiological and clinical features and well as in some cases histology. In the last decade, considerable progress has been made in the understanding of IPF clinical management, with the availability of two drugs, pirfenidone and nintedanib, that decrease pulmonary lung function decline. However, current IPF therapies only slow disease progression and prognosis remains poor. Fortunately, there are multiple clinical trials ongoing with potential new therapies targeting different disease pathways. This review provides an overview of IPF epidemiology, current insights in pathophysiology, diagnostic and therapeutic management approaches. Finally, a detailed description of current and evolving therapeutic approaches is also provided.