The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review.

BACKGROUND: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR). METHODS: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported. RESULTS: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns. CONCLUSIONS: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

Process mining to optimize palliative patient flow in a high-volume radiotherapy department.

INTRODUCTION: In radiotherapy, palliative patients are often suboptimal managed and patients experience long waiting times. Event-logs (recorded local files) of palliative patients, could provide a continuative decision-making system by means of shared guidelines to improve patient flow. Based on an event-log analysis, we aimed to accurately understand how to successively optimize patient flow in palliative care. METHODS: A process mining methodology was applied on palliative patient flow in a high-volume radiotherapy department. Five hundred palliative radiation treatment plans of patients with bone and brain metastases were included in the study, corresponding to 290 patients treated in our department in 2018. Event-logs and the relative attributes were extracted and organized. A process discovery algorithm was applied to describe the real process model, which produced the event-log. Finally, conformance checking was performed to analyze how the acquired event-log database works in a predefined theoretical process model. RESULTS: Based on the process discovery algorithm, 53 (10%) plans had a dose prescription of 8 Gy, 249 (49.8%) plans had a dose prescription of 20 Gy and 159 (31.8%) plans had a dose prescription of 30 Gy. The remaining 39 (7.8%) plans had different dose prescriptions. Considering a median value, conformance checking demonstrated that event-logs work in the theoretical model. CONCLUSIONS: The obtained results partially validate and support the palliative patient care guideline implemented in our department. Process mining can be used to provide new insights, which facilitate the improvement of existing palliative patient care flows.

Gastrointestinal stromal tumors and second primary malignancies: a retrospective monocentric analysis.

In the post-Imatinib era, the median survival of patients diagnosed with GIST has reached almost 5 years. Prolonging GIST-specific survival, GIST patients have an increased incidence of secondary neoplasia. Data on the prognostic impact of second tumors in GIST patients are very poor with few and small retrospective analyses available in the literature. We conducted a retrospective monocentric analysis on 145 patients diagnosed with GIST between April 2001 and October 2018. Kaplan-Meier and Cox hazard methods were used for survival analysis. A total of 154 GIST patients were included and 31 patients of them (21%) were diagnosed with at least one additional malignancy. The most common second tumors associated with GIST were gastrointestinal tumors. GIST patients with additional malignancies showed to have lower size (>5 cm: 35% vs 45%; p=0.75), higher mitotic rate (>5/50 HPFs: 42% vs 29%; p=0.24), higher presence of c-KIT mutation (85% vs 69%), a lower presence of PDGFRα mutation (8% vs 17%; p=0.05) and shorter survival (mOS: 9.6 vs 15.5 years; p=0.30). In conclusion, our study did not find any significant correlation between clinicopathological characteristics and the development of a second tumor in GIST patients. Further analyses and strict follow up protocols are needed in order to early diagnose and promptly treat a second primary tumor in the GIST population.

Immunoglobulin A antibodies to oxidized collagen type II as a potential biomarker for the stratification of spondyloarthritis from rheumatoid arthritis.

OBJECTIVES: The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA). METHOD: Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs. CONCLUSION: Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.

Ultraviolet radiation in the Atacama Desert.

The world's highest levels of surface ultraviolet (UV) irradiance have been measured in the Atacama Desert. This area is characterized by its high altitude, prevalent cloudless conditions, and a relatively low total ozone column. In this paper, we provide estimates of the surface UV (monthly UV index at noon and annual doses of UV-B and UV-A) for all sky conditions in the Atacama Desert. We found that the UV index at noon during the austral summer is expected to be greater than 11 in the whole desert. The annual UV-B (UV-A) doses were found to range from about 3.5 kWh/m2 (130 kWh/m2) in coastal areas to 5 kWh/m2 (160 kWh/m2) on the Andean plateau. Our results confirm significant interhemispherical differences. Typical annual UV-B doses in the Atacama Desert are about 40% greater than typical annual UV-B doses in northern Africa. Mostly due to seasonal changes in the ozone, the differences between the Atacama Desert and northern Africa are expected to be about 60% in the case of peak UV-B levels (i.e. the UV-B irradiances at noon close to the summer solstice in each hemisphere). Interhemispherical differences in the UV-A are significantly lower since the effect of the ozone in this part of the spectrum is minor.

Jaccoud's arthropathy, an unusual manifestation of idiopathic retroperitoneal fibrosis: rapid improvement of symptoms after tocilizumab treatment.

Jaccoud's arthropathy (JA) is a chronic, non erosive, rheumatoid-like deformity associated with rheumatic fever (RF) and systemic lupus erythematosus and with other diseases such as psoriatic arthritis, connective tissue diseases, hypocomplementemic urticarial vasculitis, infections, sarcoidosis and neoplasia. We described a case of JA in a patient with cutaneous psoriasis but with a particular disease evolution associated with idiopathic retropritoneal fibrosis (IRF), evaluated with computed tomography, magnetic resonance and 18F-FDG PET/ CT. The patient, following failure with steroids, methotrexate and etanercept, was treated with tocilizumab (8 mg/kg) once every 4 weeks for 6 months. A rapid improvement of symptoms and disappearance of 18F-FDG uptake was shown. We describe a review of literature of rheumatic manifestations of IRF and the possible role of interleukin-6 in the pathway of JA and IRF.

PRODIGE: PRediction models in prOstate cancer for personalized meDIcine challenGE.

AIM: Identifying the best care for a patient can be extremely challenging. To support the creation of multifactorial Decision Support Systems (DSSs), we propose an Umbrella Protocol, focusing on prostate cancer. MATERIALS & METHODS: The PRODIGE project consisted of a workflow for standardizing data, and procedures, to create a consistent dataset useful to elaborate DSSs. Techniques from classical statistics and machine learning will be adopted. The general protocol accepted by our Ethical Committee can be downloaded from cancerdata.org . RESULTS: A standardized knowledge sharing process has been implemented by using a semi-formal ontology for the representation of relevant clinical variables. CONCLUSION: The development of DSSs, based on standardized knowledge, could be a tool to achieve a personalized decision-making.

Leiomiomatosis intravenosa de localización cervicovaginal / Intravenous cervicovaginal Leiomyomatosis

La leiomiomatosis intravenosa (LIV) es una patología poco frecuente caracterizada por la presencia de músculo liso en las venas miometriales del cuerpo uterino. Se presenta un caso de LIV limitado a cuello uterino y manguito vaginal. Se realizó histerectomía total con diagnóstico prequirúrgico de miomatosis uterina y menometrorragia. El diagnóstico de LIV fue anatomopatológico mediante técnicas de inmunohistoquímica. Si bien el 70 por ciento de las pacientes con LIV pueden ser curadas con cirugía, en un 30 por ciento de los casos existe persistencia o recurrencia a distancia de la enfermedad. En nuestro caso los controles a treinta meses de la cirugía fueron negativos e incluyeron estudios cardiovasculares, pulmonares, hepáticos y cerebrales.

Intravenous leiomyomatosis (IVL) cervicovaginal is an uncommon pathology, characterized by the presence of sooth muscle in the myometrial veins of the uterine body. A case of IVL is reported, limited to the cervix uteri and the vaginal muff. A total hysterctomy was performed, with presurgical diagnosis of uterine myomatosis and menometrorrhagia. The diagnosis of IVL was performed by clinicopathological analysis and by immunohistochemistry techniques. Although the 70 percent of the patients with IVL can be cured by surgery, in a 30 percentof the cases, there exists persistence and recurrency at distancy from the disease. In our case, the controls after 30 months since surgery were negatives, and included cardiovascular, pulmonary, hepatic and cerebral studies.

Evaluación de calidad de vida pre y posquirúrgica en pacientes con prolapso de compartimiento anterior y posterior / Evaluation of the quality of life outcomes for women with genital tract prolapses

Objetivos: Demostrar la utilidad de un inventario sobe calidad de vida para evaluar síntomas pre y postquirúrgicos en pacientes con prolapso anteior y posterior. Pacientes y métodos: Estudio retrospectivo, longitudinal, comparativo. Enero 2009-diciembre 2010. Se incluyeron 26 ptes, prom: 63 años con prolapso ant (EIII) y post (EII). Tratamiento: colporrafia anterior con malla subvesical y colpoperineorrafia. Evaluación de síntomas genitales, miccionales y defecatorios pre y postquirúrgicos con "Inventario de molestias por trastornos del piso pélvico" de Barber. Se utilizá Prueba Mc Nemar para variables cualitativas. Nivel de significación estadístico p=0.05. Resultados: Síntomas vaginales: preQ en el 100 por ciento. Los más frecuentes: pesadez y bulto vaginal que se redujeron en el postQ a 7 por ciento (p=0,000). Síntomas miccionales: preQ en el 84 por ciento. Los más frecuentes: a) sensación de vaciamiento incompleto de vejiga 77 por ciento que se redujo al 9 por ciento en postQ (P=0,001) y b) Aumento de la frecuencia miccional 68 por ciento que se redujo al 45 por ciento (p=0,063) Sintomas defecatorios preQ 46 por ciento. Los más frecuentes: a) necesidad de aumentar esfuerzo defecatorio 58 por ciento se redujo al 41 por ciento en postQ (P=0500) y b) maniiobras para completar la defecación 33 por ciento que desapareció en postQ (p=0.12). Conclusiones: mediante la utilización del Inventario se pudo comprobar que los resultados fueron estadísticamente significativos para los síntomas vaginales y para los miccionales de vaciado incompleto. El resto de los síntomas a pesar de no ser significativos evidenciaron mejoría en el postoperatorio.

Women with pelvic floor disorders show a negative impact on their quality of life questionnaires. The aim of the present report, was to demonstrate the usefulness of a quality of life questionnaire, to evaluate both pre and postsurgical outcomes in patients with anterior or posterior prolapses. Conclusion: the employement of an Inventary could arrive to the demonstration that the results were statistically significative for the vaginal symptons and for the micturation of incomplete emptiness. The rest of the symptons, despite that they were not significatives, showed improvement during the outcomes.

The effect of etanercept on hepatic fibrosis risk in patients with non-alcoholic fatty liver disease, metabolic syndrome, and psoriasis.

BACKGROUND: Patients with psoriasis show a greater prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than their counterparts with NAFLD and without psoriasis. The link between these three pathological conditions is a chronic low-grade inflammatory status. In this study, we aimed to evaluate the effect of etanercept versus psoralen and UVA (PUVA) therapy on the hepatic fibrosis risk in patients with psoriasis, metabolic syndrome, and NAFLD (with NAFLD diagnosed by ultrasonography). METHODS: Eighty-nine patients with chronic moderate-to-severe plaque-type psoriasis, metabolic syndrome, and NAFLD received etanercept or PUVA treatment. The two groups of patients were compared for anthropometric variables (body mass index and waist/hip ratio), lipid profile, glucose homeostasis, inflammatory status, risk of hepatic fibrosis, and ultrasonographic aspect of the liver, both at baseline (time [T] 0) and after 24 weeks of treatment (T24). RESULTS: After 24 weeks of treatment, only in the group receiving etanercept, we detected significant reductions (p < 0.05) in the aspartate transaminase (AST)/alanine transaminase (ALT) ratio, C-reactive protein (CRP) serum levels, fasting insulin levels, and homeostasis model assessment (HOMA) index, and a significant increase in the Quantitative Insulin-Sensitivity Check Index (QUICKI) (p < 0.05). CONCLUSIONS: In patients with psoriasis, metabolic syndrome, and NAFLD, the risk of the development of hepatic fibrosis seems to be directly correlated with insulin resistance. Etanercept could be more efficacious to reduce the risk of developing hepatic fibrosis than PUVA therapy, and this preventive effect could be related to its anti-inflammatory and glucose homeostatic properties. We note that a limitation of the study was that the diagnosis of NAFLD was conducted by ultrasonography.

Isobaric gasless laparoscopic myomectomy for removal of large uterine leiomyomas.

BACKGROUND: This study aimed to evaluate the feasibility and safety of isobaric laparoscopic removal of large myomas (> or = 8 cm) using the Laparotenser, a subcutaneous abdominal wall-lifting system. METHODS: A series of 63 consecutive patients with at least one large symptomatic subserosal or intramural uterine myoma (> or = 8 cm) underwent an isobaric gasless laparoscopic myomectomy. Conventional laparotomy instruments were used. RESULTS: The procedure was successfully completed for all 63 consecutive patients. The average size of the dominant myoma was 11 cm. The mean number of myomas removed from each patient was 3.6. The mean blood loss was 143 ml, and the mean operating time was 72 min. No intraoperative complication occurred. CONCLUSIONS: Gasless laparoscopic myomectomy for the removal of large myomas using the Laparotenser is feasible and safe. It offers several advantages over laparoscopy with pneumoperitoneum.

Identification of the products of the equine herpesvirus type 4 gI and gE genes.

In order to identify the products of the equine herpesvirus type 4 (EHV-4) gI and gE genes, we have constructed recombinant vaccinia viruses containing the putative gI or gE genes. These recombinant viruses synthesized EHV-4 gI and gE with apparent molecular masses of 75 and 80kDa, respectively. Antibodies raised against both recombinant viruses detected a 75 kDa gI and a 95 kDa gE in EHV-4-infected cells. The results also suggest that the EHV-4 gI and gE would form a complex like in other herpesviruses.

A deletion in the gI and gE genes of equine herpesvirus type 4 reduces viral virulence in the natural host and affects virus transmission during cell-to-cell spread.

In order to identify the role of the equine herpesvirus type 4 (EHV-4) glycoprotein I (gI) and E (gE) genes in determining viral virulence and their affect on the infection cycle, we constructed an EHV-4 recombinant strain containing a deletion in both gI and gE genes and its revertant. The recombinant was assayed in vitro in order to compare its growth kinetics with the parent and revertant viruses. Our results indicated that a deletion in the genes encoding gI and gE affected cell-to-cell spread of the virus in vitro. In order to assess the pathogenicity and vaccine efficacy of the recombinant in a natural host, colostrum-deprived foals were inoculated intranasally with the recombinant. Clinical signs obtained in foals upon the inoculation with the recombinant were milder than that for the revertant. This suggests that intact gI and/or gE genes are important factors in the expression of virulence in EHV-4 as in seen in the case of other herpesviruses. In addition, full protection against challenge infection was observed in foals, which had undergone a previous inoculation of the recombinant.

Transcriptional analyses of the region of the equine herpesvirus type 4 genome encoding glycoproteins I and E.

To map the transcripts encoding the equine herpesvirus type 4 (EHV-4) glycoproteins I (gI) and E (gE), transcriptional analyses were performed at the right part of the unique short segment of EHV-4 genome. The results revealed that the gI gene is encoded by a 1.6-kb transcript which is 3' coterminal with a 3.0-kb gD mRNA while the gE gene is encoded by two transcripts of 3.5- and 2.4-kb in size. The transcriptional patterns described in this study for the EHV-4 gI and gE are similar to those found in the equivalent region of herpes simplex virus type 1 and feline herpesvirus type 1. Characterization of EHV-4 gI and gE glycoprotein genes may facilitate future studies to define their roles in the EHV-4 infection.

Further development of a recombinant feline herpesvirus type 1 vector expressing feline calicivirus immunogenic antigen.

We previously reported the attenuation of thymidine kinase (TK) deficient mutant (C7301dlTK) of feline herpesvirus type 1 (FHV-1) in cats and the construction of a recombinant FHV-1 (C7301dlTK-Cap) inserted a precursor capsid gene of feline calcivirus (FCV) into the TK deletion locus of the C7301dlTK. In this study, we constructed a further improved recombinant FHV-1 (dlTK(gCp)-Cap) carrying a putative FHV-1 gC promoter sequence upstream of the FCV precursor capsid gene of the C7301dlTK-Cap. Growth kinetics of the dlTK(gCp)-Cap in cell cultures was similar to those of C7301dlTK and C7301dlTK-Cap. A strong expression of FCV immunogenic antigen by dlTK(gCp)-Cap was confirmed by indirect immunofluorescence and enzyme-linked immunosorbent assays. In addition, one vaccination with dlTK(gCp)-Cap protected cats more effective against subsequent virulent FCV challenge than that with C7301dlTK-Cap.

Nucleotide sequences of glycoprotein I and E genes of equine herpesvirus type 4.

The nucleotide sequences of the glycoprotein I (gI) and E (gE) genes of equine herpesvirus type 4 (EHV-4) strain TH20 were determined. The predicted region encoding the EHV-4 gI gene is 1,263 nucleotides, corresponding to a polypeptide of 420 amino acids in length. The predicted region encoding the EHV-4 gE gene is 1,647 nucleotides, corresponding to a polypeptide of 548 amino acids in length. The EHV-4 gI and gE genes show 74% and 85% identity at the amino acid level with those of equine herpesvirus type 1 (EHV-1), respectively. Furthermore, we have found an open reading frame homologous to the EHV-1 gene 75, which overlaps in part with the 3' end of EHV-4 gE gene. These sequence data will be useful for development of a modified live vaccine against equine herpesvirus type 1 and 4 infections.

An equine herpesvirus type 1 recombinant with a deletion in the gE and gI genes is avirulent in young horses.

The cell culture-adapted KyA strain of equine herpesvirus type 1 (EHV-1) has been found to be attenuated in young horses (Matsumura et al., 1996, Vet. Microbiol. 48, 353-365). The KyA strain lacks at least six genes in its genome, including those encoding glycoproteins gE and gI. To elucidate whether EHV-1 glycoproteins gE and gI play a role in viral virulence, we have constructed an EHV-1 recombinant that has the genes encoding both gE and gI deleted from its genome and its revertant. Growth properties of the deletion mutant virus in vitro were compared with those of the parent and the revertant viruses. Plaque size of the mutant virus in fetal horse kidney (FHK) cells was significantly smaller than those of the parent and the revertant viruses. In one-step growth experiments, however, the yields of infectious virus from FHK cells infected with the deletion mutant, the parent, or the revertant virus were approximately the same. The results suggested that gE and/or gI of EHV-1 promoted cell-to-cell spread of the virus, but that these glycoproteins were not involved in the process of virus maturation and release or in virus attachment and penetration. Subsequently, the virulence of mutant and revertant viruses was examined in young horses. No clinical signs were observed in six horses, including three colostrum-deprived foals inoculated intranasally with the deletion mutant virus, whereas three colostrum-deprived foals inoculated intranasally with the revertant virus manifested clinical signs typical for EHV-1 respiratory infection (i.e., pyrexia, nasal discharge, and swelling of submandibular lymph nodes). The results obtained from in vivo studies revealed that the EHV-1 mutant defective in both gE and gI genes was avirulent in young horses, suggesting that gE and/or gI of the EHV-1 have an important role in EHV-1 virulence. However, the EHV-1 mutant defective in both gE and gI genes induced only a partial protectivity in inoculated foals from manifestation of respiratory symptoms after challenge infection.

Anterior cruciate ligament patellar tendon reconstruction: it is probably better to leave the tendon defect open!

The purpose of our prospective study was to establish whether or not in anterior cruciate ligament (ACL) patellar tendon reconstruction the tendon defect has to be closed. In 50 consecutive ACL patellar tendon reconstructions, the tendon defect was randomly closed (group I) or left open (group II). The following data were recorded from all patients on the 4th and 14th days post operation: range of motion (ROM), pain at rest, pain and validity at isometric contraction, ability of bent leg raising (at 4th day) and straight leg raising (at 14th day). All the patients underwent ultrasonographic examination after 3 months and X-ray scanning at 6 months post operation. Forty patients underwent a CT-scan examination at 6 months. Thirty patients underwent isokinetic testing between 10 and 12 months post operation. Evaluating the immediate post operation data, no statistically significant differences emerged between the two groups. Ultrasonography showed in 68% of the knees of group I (defect closed) a thickened patellar tendon (PT), while in 60% of group II it was of normal thickness. No patients of either group developed patella infera by X-ray evaluation 6 months post operation. CT scans at 6 months showed that 100% of the knees of group I had a thickened PT in toto (nearly twice as thick as normal). Scar tissue was present not only in its central third but also in more than half of the cases in the medial and lateral third. In group II 75% of the patients had a normal thickness PT and 25% presented with only a minimal thickening. Scar tissue was distinguished only at its central third.(ABSTRACT TRUNCATED AT 250 WORDS)