Molecular maps of synovial cells in inflammatory arthritis using an optimized synovial tissue dissociation protocol.

In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells from 25 synovial tissues affected by inflammatory arthritis, including 16 structural, 11 lymphoid, and 15 myeloid cell clusters. This synovial cell map expanded the diversity of synovial cell types/states, detected synovial neutrophils, and broadened synovial endothelial cell classification. We revealed tissue-resident macrophage subsets with proposed matrix-sensing (FOLR2+COLEC12high) and iron-recycling (LYVE1+SLC40A1+) activities and identified fibroblast subsets with proposed functions in cartilage breakdown (SOD2highSAA1+SAA2+SDC4+) and extracellular matrix remodeling (SERPINE1+COL5A3+LOXL2+). Our study offers an efficient synovium dissociation method and a reference scRNA-seq resource, that advances the current understanding of synovial cell heterogeneity in inflammatory arthritis.

Non-exposed endoscopic wall-inversion surgery with one-step nucleic acid amplification for early gastrointestinal tumors: Personal experience and literature review.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery is a safe, organ-sparing surgery that achieves full-thickness resection with adequate margins. Recent studies have demonstrated the safety and efficacy of these procedures. However, these techniques are limited by the exposure of the tumor and mucosa to the peritoneal cavity, which could lead to viable cancer cell seeding and the spillage of gastric juice or enteric liquids into the peritoneal cavity. Non-exposed endoscopic wall-inversion surgery (NEWS) is highly accurate in determining the resection margins to prevent intraperitoneal contamination because the tumor is inverted into the visceral lumen instead of the peritoneal cavity. Accurate intraoperative assessment of the nodal status could allow stratification of the extent of resection. One-step nucleic acid amplification (OSNA) can provide a rapid method of evaluating nodal tissue, whilst near-infrared laparoscopy together with indocyanine green can identify relevant nodal tissue intraoperatively. AIM: To determine the safety and feasibility of NEWS in early gastric and colon cancers and of adding rapid intraoperative lymph node (LN) assessment with OSNA. METHODS: The patient-based experiential portion of our investigations was conducted at the General and Oncological Surgery Unit of the St. Giuseppe Moscati Hospital (Avellino, Italy). Patients with early-stage gastric or colon cancer (diagnosed via endoscopy, endoscopic ultrasound, and computed tomography) were included. All lesions were treated by NEWS procedure with intraoperative OSNA assay between January 2022 and October 2022. LNs were examined intraoperatively with OSNA and postoperatively with conventional histology. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. Data were collected prospectively and analyzed retrospectively. RESULTS: A total of 10 patients (5 males and 5 females) with an average age of 70.4 ± 4.5 years (range: 62-78 years) were enrolled in this study. Five patients were diagnosed with gastric cancer. The remaining 5 patients were diagnosed with early-stage colon cancer. The mean tumor diameter was 23.8 ± 11.6 mm (range: 15-36 mm). The NEWS procedure was successful in all cases. The mean procedure time was 111.5 ± 10.7 min (range: 80-145 min). The OSNA assay revealed no LN metastases in any patients. Histologically complete resection (R0) was achieved in 9 patients (90.0%). There was no recurrence during the follow-up period. CONCLUSION: NEWS combined with sentinel LN biopsy and OSNA assay is an effective and safe technique for the removal of selected early gastric and colon cancers in which it is not possible to adopt conventional endoscopic resection techniques. This procedure allows clinicians to acquire additional information on the LN status intraoperatively.

Right colon cancer: The influence of specific location on recurrence and survival.

AIM: This study aimed to investigate whether the site of the tumour within the right colon affects survival in patients who underwent right colectomy for colon cancer. METHODS: An observational retrospective longitudinal study was performed in patients who underwent right colectomy for non-metastatic, invasive right-sided colon cancer. Patients were categorized into two groups based on tumour location: (i) caecum and ascending colon; (ii) hepatic flexure and proximal transverse colon. Demographic and clinical features were characterized, and a survival analysis was performed. RESULTS: Of the 198 patients enroled in the study, 134 (67.8%) had caecal or ascending colon cancer and 64 (32.3%) had hepatic flexure or transverse colon cancer. Seventy (35.4%) were female and the mean age at the time of surgery was 71.6 (SD 11.4). The groups were comparable with respect to the number of lymph nodes sampled, the pTNM stage, the histological differentiation grade and the likelihood of patients receiving adjuvant chemotherapy. Recurrence rate was nearly twice as high in the hepatic flexure and proximal transverse colon group (12.5% vs 6.7%), but this difference was not statistically significant (p = 0.174). Kaplan-Meier analysis showed no differences in disease-free (p = 0.255) and overall survival (p = 0.258) between the groups. CONCLUSION: In our population, specific location of right-sided colon cancers does not appear to have an influence on survival. Further investigation is needed to determine if tumour subsite has an impact on the recurrence rate, and whether it should be considered in defining prognosis and treatment.

Determinantes sociais de saúde da população em situação de rua vulnerável à tuberculose / Social determinants of health of the homeless population vulnerable to tuberculosis / Determinantes sociales de la salud de la población sin hogar vulnerable a la tuberculosis

Objetivo: analisar determinantes sociais de saúde da população em situação de rua vulnerável à tuberculose. Métodos: estudo descritivo, exploratório de abordagem quantitativa. A coleta ocorreu entre julho e dezembro de 2017, com pessoas em situação de rua de dois municípios da região metropolitana do Cariri, utilizando um instrumento de elaboração própria. A análise foi delineada considerando o modelo de Dahlgren e Wintehead para os determinantes sociais em saúde. Resultados: Foram entrevistadas 70 pessoas, com predomínio do sexo masculino, idade entre 18 e 32 anos, raça/cor parda e baixa escolaridade. Grande parte afirmou ser tabagistas, fazer uso de álcool, não utilizar medicamentos, manter contato com suas famílias e possuir condições de vida e trabalho precárias, a maioria indicando as condições financeiras muito baixas como motivo para morar na rua. Relataram buscar a atenção primária como serviço de saúde e não utilizavam serviços do governo, apesar de terem renda inferior a um salário. As pessoas que referiram tosse realizaram baciloscopia, porém todos obtiveram resultado negativo para tuberculose. Conclusão: A identificação dos determinantes sociais em saúde é importante para conhecer as demandas de saúde da população em situação de rua e possibilita o fortalecimento das políticas de combate às fragilidades que essas pessoas estão expostas. (AU)

Objective: To analyze social determinants of health of homeless population vulnerable to tuberculosis. Methods: Descriptive, exploratory study with a quantitative approach. The collection occurred between July and December 2017, with homeless people from two municipalities of the metropolitan region of Cariri, using an instrument of its own elaboration. The analysis was designed considering the model of Dahlgren and Wintehead for the social determinants of health. Results: 70 people were interviewed, predominantly male, aged between 18 and 32 years, mixed race/color and low education level. Most of them said they were smokers, made use of alcohol, did not use medications, did not maintain contact with their families and had poor living and working conditions and pointed all of those as motives to be homeless. They declared that they seek mainly the primary health care as a service and did not use government services, in spite of having an income below one salary. The ones who reported cough underwent bacilloscopy, but all of them had a negative result for tuberculosis. Conclusion: The identification of the social determinants of health is important to know the health demands of the homeless population and enables the strengthening of policies to combat the weaknesses these people are exposed to. (AU)

Objetivo: Analizar los determinantes sociales de la salud en la población sin hogar vulnerable a la tuberculosis. Métodos: Estudio descriptivo, exploratorio con abordaje cuantitativo. La recolección se llevó a cabo entre julio y diciembre de 2017, con personas sin hogar de dos municipios de la región metropolitana del Cariri, utilizando un instrumento de su propio desarrollo. El análisis se diseñó considerando el modelo de Dahlgren y Wintehead para los determinantes sociales en salud. Resultados: Se entrevistó a 70 personas, predominantemente del sexo masculino, con edades comprendidas entre 18 y 32 años, mestizo / color y bajo nivel educativo. Una gran parte afirmó ser fumadora, consumir alcohol, no consumir medicamentos, mantener contacto con sus familias y tener condiciones de vida y de trabajo precarias, la mayoría indicando condiciones económicas muy bajas como razón para vivir en la calle. Informaron que buscan principalmente la atención primaria como servicio de salud y no utilizan los servicios gubernamentales, a pesar de tener ingresos inferiores a un salario. Las personas que informaron tos se sometieron a una baciloscopia, pero todas tuvieron un resultado negativo para la tuberculosis. Conclusión: La identificación de los determinantes sociales en salud es importante para comprender las demandas de salud de la PSR y posibilita el fortalecimiento de políticas para combatir las debilidades a las que están expuestas estas personas. (AU)

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials.

BACKGROUND: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. METHODS: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)-European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). FINDINGS: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47-2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). INTERPRETATION: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response. FUNDING: UK Medical Research Council and Versus Arthritis.

Laparoscopic and endoscopic cooperative surgery for full-thickness resection and sentinel node dissection for early gastric cancer.

The endoscopic submucosal dissection (ESD) technique has become the gold standard for submucosal tumors that have negligible risk of lymph node metastasis (LNM), due to its minimal invasiveness and ability to improve quality of life. However, this technique is limited in stage T1 cancers that have a low risk of LNM. Endoscopic full thickness resection can be achieved with laparoscopic endoscopic cooperative surgery (LECS), which combines laparoscopic gastric wall resection and ESD. In LECS, the surgical margins from the tumor are clearly achieved while performing organ-preserving surgery. To overcome the limitation of classical LECS, namely the opening of the gastric wall during the procedure, which increases the risk of peritoneal tumor seeding, non-exposed endoscopic wall-inversion surgery was developed. With this full-thickness resection technique, contact between the intra-abdominal space and the intragastric space was eliminated.

Portuguese recommendations for the use of biological and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis - 2020 update.

OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Rectal duplication cyst in an adult with a history of imperforate anus: a diagnostic challenge.

Rectal duplications are rare congenital anomalies that represent 1%-6% of alimentary tract duplications. We report a case of a woman in her 50s who presented to our hospital with perianal pain and urinary retention. She had a history of imperforate anus repaired after birth and dynamic graciloplasty performed during her adulthood for faecal incontinence. Abdominal CT scan showed a fluid collection extending from the electrostimulator, placed in a subcutaneous pocket in the abdomen, to the rectouterine pouch. Infection related to the electrostimulator was assumed and, after a course of antibiotics without patient improvement, the electrostimulator was removed. The symptoms and the pelvic fluid collection persisted, and diagnostic laparoscopy was performed. Diagnosis of rectal duplication cyst was made intraoperatively, and the cyst was completely resected. Patient fully recovered after surgery. This is a rare case of a rectal duplication cyst presenting during adulthood and associated with imperforate anus.

Prognostic value of inflammation-based prognostic scores in patients with colorectal cancer

Background: Anatomopathological staging is the primary method to determine the prognosis of patients with colorectal carcinoma (CRC). However, new tools have been developed that can complement it, such as the analysis of the elevation of systemic inflammatory markers. Objective: To evaluate the impact of the elevation of scores based on inflammatory markers (the neutrophil-to-lymphocyte ratio [NLR], the Glasgow Prognostic Score [GPS], and isolated C-reactive protein [CRP]) in the prognosis of patients diagnosed with CRC and submitted to potentially curative surgery in Hospital de Braga, Portugal, between January 1st, 2005, and December 31st, 2010. Methods: A retrospective analysis of the data of 426 patients was performed, with a collection of several clinico-pathological variables, as well as the levels of lymphocytes, neutrophils, albumin and CRP, in the pre- and postoperative periods, to apply the different scores to the sample. Results: From the analysis of the survival curves, we concluded that patients with increased NLR in the pre- and postoperative periods present a lower cancer-related survival than patients with normal NLR (preoperative period: 93.7 versus 122 months; p<0.001; postoperative period: 112 versus 131 months; p=0.002). Patients with increased NLR in the pre- and postoperative periods also had a lower disease-free survival (preoperative period: 88.0 versus 122 months; p<0.001; postoperative period: 111 versus 132 months; p=0.002). In addition, increased pre- and postoperative NLR was associatedwith a higher risk of death due to CRC (preoperatively: hazard ratio [HR]=2.25; p<0.001; postoperatively: HR=2.18; p=0.003). However, the multivariate analysis shows that only postoperative NLR (ajusted HR =2.66; p=0.002) does so independently of the remaining variables. Conclusion: Regarding the scores applied to the sample, the NLR was the one that most consistently related to the prognosis of the patients. However, it would be useful to develop a prospective study that could confirm this relationship. (AU)

Gastric Adenocarcinoma Presenting as a Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibody-Positive Polyarthritis: A Case Report and Review of Literature.

A 64-year-old male presented with a 6-month history of symmetric polyarthritis involving proximal interphalangeal joints and metacarpophalangeal joints of the hands, wrists, and ankles. Associated symptoms included vomiting, progressive fatigue, and weight loss. Laboratory results showed microcytic anemia, leukocytosis, thrombocytosis, elevated C-reactive protein and erythrocyte sedimentation rate, and rheumatoid factor (RF) and anti-cyclic citrullinated protein (ACPA) antibody positivity. Joints radiographs were normal, without erosions. Upper endoscopy and gastric endoscopic ultrasonography showed a gastric adenocarcinoma with lymphatic involvement. Intraoperatively, peritoneal carcinomatosis was documented, and the patient started palliative chemotherapy. A paraneoplastic seropositive arthritis was assumed, and treatment with low-dose prednisolone and hydroxychloroquine was started. Arthritis remission was achieved and sustained up to 18 months of follow-up, although gastric cancer progression was documented. We describe a unique phenotype of paraneoplastic arthritis (PA) presenting as a seropositive (RF and ACPA positivity) rheumatoid arthritis (RA) with a good response to both low dose corticosteroids and hydroxychloroquine therapy. We also review the literature of PA, mostly the RA-like pattern, and the association between PA and ACPA positivity. This case highlights the importance of considering underlying cancer in elderly male patients, presenting with polyarthritis and systemic symptoms, even in those with ACPA-positive RA-like arthritis.

Safety and Effectiveness of Biologic Disease-Modifying Antirheumatic Drugs in Older Patients with Rheumatoid Arthritis: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: The number of older patients with rheumatoid arthritis is increasing, but data on drug effectiveness and safety in these patients are scarce. This study assessed the effectiveness and safety of biologic disease-modifying antirheumatic drugs in older patients with rheumatoid arthritis. METHODS: This prospective cohort study was based on data recorded in the Rheumatic Diseases Portuguese Register (Reuma.pt). Treatment persistence, European League Against Rheumatism response at 6 and 12 months, and adverse events were compared between adult (age < 65 years), old (age 65-74 years), and very old (age ≥ 75 years) patients. RESULTS: In total, 2401 patients were included, of which 379 were old and 83 were very old. Older patients had higher disease activity at baseline (Disease Activity Score 28: 5.5 in adults, 5.7 in old patients, and 6 in very old patients; p = 0.02) and more comorbidities, with patients aged 65-74 years beginning biologic disease-modifying antirheumatic drugs later in the course of rheumatoid arthritis. Treatment persistence was similar in the three patient groups (p = 0.07). The European League Against Rheumatism response rates were comparable in the three groups at 6 months (81.6% of adults, 75.2% of old patients, and 81.8% of very old patients; p = 0.19), and inferior in old patients at 12 months. The proportion of patients who experienced adverse events was also similar in the three groups (21% of adults, 22.5% of old patients, and 22.9% of very old patients; p = 0.76), but the rate of serious adverse events was higher in old patients (1.94/100 patient-years) and very old patients (4.29/100 patient-years) compared with 1.03/100 patient-years in adult patients with rheumatoid arthritis (p < 0.05). CONCLUSIONS: Adults, old patients, and very old patients with rheumatoid arthritis benefit similarly from biologic disease-modifying antirheumatic drug treatments, although older patients have more active disease at baseline and more comorbidities. However, it is necessary to consider the risk of serious adverse events in older patients when prescribing a biologic.

COVID-19 and the Global Impact on Colorectal Practice and Surgery.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 virus that emerged in December 2019 causing coronavirus disease 2019 (COVID-19) has led to the sudden national reorganization of health care systems and changes in the delivery of health care globally. The purpose of our study was to use a survey to assess the global effects of COVID-19 on colorectal practice and surgery. MATERIALS AND METHODS: A panel of International Society of University Colon and Rectal Surgeons (ISUCRS) selected 22 questions, which were included in the questionnaire. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in the ISUCRS database and was advertised on social media sites. The questionnaire remained open from April 16 to 28, 2020. RESULTS: A total of 287 surgeons completed the survey. Of the 287 respondents, 90% were colorectal specialists or general surgeons with an interest in colorectal disease. COVID-19 had affected the practice of 96% of the surgeons, and 52% were now using telemedicine. Also, 66% reported that elective colorectal cancer surgery could proceed but with perioperative precautions. Of the 287 respondents, 19.5% reported that the use of personal protective equipment was the most important perioperative precaution. However, personal protective equipment was only provided by 9.1% of hospitals. In addition, 64% of surgeons were offering minimally invasive surgery. However, 44% reported that enough information was not available regarding the safety of the loss of intra-abdominal carbon dioxide gas during the COVID-19 pandemic. Finally, 61% of the surgeons were prepared to defer elective colorectal cancer surgery, with 29% willing to defer for ≤ 8 weeks. CONCLUSION: The results from our survey have demonstrated that, globally, COVID-19 has affected the ability of colorectal surgeons to offer care to their patients. We have also discussed suggestions for various practical adaptation strategies for use during the recovery period.

Considerations for improving quality of care of patients with rheumatoid arthritis and associated comorbidities.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5-1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities. METHODS: A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse. RESULTS: Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice. CONCLUSION: Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.