Continuous monitoring after laparoscopic Roux-En-Y gastric bypass: a pathway to ambulatory care surgery - a pilot study.

Same-day discharge (SDD) after Laparoscopic Roux-En-Y Gastric Bypass (LRYGB) faces resistance due to possible undetected postoperative complications. These present with changes in vital signs, which continuous remote monitoring devices can detect. This study compared continuous vital signs monitoring using the Isansys Patient Status Engine™ with standard nursing vital signs measurements to assess the device's reliability in postoperative surveillance of patients undergoing LRYGB. We conducted a pilot study including patients who underwent LRYGB. During their hospital stay, patients were continuously monitored using the Isansys Patient Status Engine™ with Lifetouch™, Lifetemp™, and Nonin Pulse Oximeter™ sensors. The heart rate (HR), body temperature, and oxygen saturation (SpO2) collected by the device were compared with standard nursing assessments. Thirteen patients with a mean body mass index of 41.5 ± 4.4 kg/m2 were included. No major complications occurred. The median HR assessed by standard and continuous monitoring did not significantly differ (75.5 [69-88] vs. 77 [66-91] bpm, p = 0.995), nor did the mean values of SpO2 (94.7 ± 2.0 vs. 93.7 ± 1.8%, p = 0,057). A significant difference was observed in median body temperature between the nursing staff and the monitoring device (36.3 [36.1-36.7] vs. 36.1 [34.5-36.6] degrees Celsius, p = 0.012), with a tendency for lower temperature measurements by the device. In conclusion, this is the first study on continuous postoperative surveillance using the Isansys Patient Status Engine™ monitoring device for LRYGB patients. Our results introduce a novel tool for more efficient surgery. Prospective randomized experimental studies are warranted to evaluate this method's efficacy and safety.

Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.

Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.

Evaluating Surgical Outcomes and Survival in Colon Cancer Patients Over 80 Years Old.

BACKGROUND AND AIMS: In the context of an increasing older population, knowing the surgical outcomes of older patients is of paramount importance to define a comprehensive strategy for colon cancer treatment in these patients. This study aimed to analyze the surgical outcomes and survival of patients over 80 years old undergoing surgery for colon cancer. MATERIALS AND METHODS: This is an observational retrospective longitudinal study of patients over 80 years old with colon cancer diagnosis who underwent surgery for this condition, between 2018 and 2021, in a Portuguese hospital. Demographic and clinical features were characterized. Kaplan-Meier method was used for survival analysis. RESULTS: Out of 90 patients in the study, 41.1% were female. The majority (56.7%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0, with a median Charlson Comorbidity Index of 7.0. Tumors were primarily located in the right colon (52.2%) and sigmoid colon (25.6%), with most patients having stage II (35.6%) or stage III (25.5%) disease. Elective surgeries accounted for 73% of procedures, and 80.0% had curative intent, with laparoscopic surgery performed in 66.7% of cases. Only 8.3% of those undergoing curative-intent procedures received adjuvant chemotherapy. Emergent admissions were associated with more advanced cancer stages, higher rates of palliative intent procedures (45.8% versus 10.6%, p < 0.001), and more open surgeries (75.0% versus 9.1%, p < 0.001) when compared to elective procedures. Postoperative mortality was higher in the emergent group (20.8% versus 10.6%), though there was no association between the type of admission and postoperative complications. Median overall survival for all patients was 36.7 (95% CI 28.1 to 45.3) months, with significant differences between curative-intent and palliative surgeries (median of 39.8 (95% CI 32.6 to 47.0) versus 10.6 (95% CI 0.67 to 20.5) months, p = 0.015). The elective group of patients had significantly better overall survival compared to the emergent group (median of 36.7 (95% CI 30.7 to 42.7) versus 11.9 (95% CI 6.0 to 17.8) months, p = 0.01). Among the patients who underwent curative-intent procedures, there were no significant differences in overall or disease-free survival between elective and emergent groups. CONCLUSIONS: Despite the increased complexity of managing older patients, particularly in emergent cases, these findings emphasize the importance of elective, curative-intent surgeries to optimize overall survival. Effective treatment strategies and perioperative management tailored to this age group are essential for improving surgical outcomes and extending survival in elderly colon cancer patients.

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.

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.

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.

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.

Comparative effectiveness and predictors of response to tumour necrosis factor inhibitor therapies in rheumatoid arthritis.

OBJECTIVES: Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not consistent. We compared their effectiveness over 1 year in a prospective cohort. METHODS: Analyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified. RESULTS: The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response. CONCLUSION: Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.

Smoking is a predictor of worse trabecular mechanical performance in hip fragility fracture patients.

Clinical risk factors (CRFs) are established predictors of fracture events. However, the influence of individual CRFs on trabecular mechanical fragility is still a subject of debate. In this study, we aimed to assess differences, adjusted for CRFs, between bone macrostructural parameters measured in ex-vivo specimens from hip fragility fracture patients and osteoarthritis patients, and to determine whether individual CRFs could predict trabecular bone mechanical behavior in hip fragility fractures. Additionally, we also looked for associations between the 10-year risk of major and hip fracture calculated by FRAX and trabecular bone mechanical performance. In this case-control study, a group of fragility fracture patients were compared with a group of osteoarthritis patients, both having undergone hip replacement surgery. A clinical protocol was applied in order to collect CRFs [body mass index (BMI), prior fragility fracture, parental history of hip fracture, long-term use of oral glucocorticoids, rheumatoid arthritis, current smoking, alcohol consumption, age and gender]. The 10-year probability of fracture was calculated. Serum bone turnover markers were determined and dual X-ray absorptiometry performed. Femoral head diameter was evaluated and trabecular bone cylinders were drilled for mechanical testing to determine bone strength, stiffness and toughness. We evaluated 40 hip fragility fracture and 52 osteoarthritis patients. Trabecular bone stiffness was significantly lower (p = 0.042) in hip fragility fracture patients when compared to osteoarthritic individuals, adjusted for age, gender and BMI. No other macrostructural parameter was statistically different between the groups. In hip fragility fracture patients, smoking habits (ß = -0.403; p = 0.018) and female gender (ß = -0.416; p = 0.008) were independently associated with lower stiffness. In addition, smoking was also independently associated with worse trabecular strength (ß = -0.323; p = 0.045), and toughness (ß = -0.403; p = 0.018). In these patients, the 10-year risk of major (r = -0.550; p = 0.012) and hip fracture (r = -0.513; p = 0.021) calculated using only CRFs was strongly correlated with femoral neck bone mineral density but not with mechanical performance. Our data showed that among fragility fracture patients active smoking is a predictor of worse intrinsic trabecular mechanical performance, and female gender is also independently associated with lower stiffness. In this population, the 10-year risk of fracture using CRFs with different weights only reflects bone mass loss but not trabecular mechanical properties.

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.

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.

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.

Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival.

OBJECTIVES: B cells play an important role in the perpetuation of RA, particularly as autoantibody-producing cells. The ICs that further develop deposit in the joints and aggravate the inflammatory process. However, B-cell contribution in the very early stage of the disease remains unknown. The main goal of this work was to determine the concentration of cytokines potentially relevant for B-cell activation in serum from very early polyarthritis patients, with <6 weeks of disease duration, who latter on evolved into very early RA (VERA). METHODS: A proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and IL-21 levels were measured by ELISA in the serum of VERA, other very early arthritis (VEA), established RA patients and controls. SF samples of established RA were also analysed. RESULTS: VERA patients have higher levels of APRIL and BAFF as compared with VEA, established RA and controls. Furthermore, APRIL and BAFF levels are also significantly elevated in RA-SF when compared with serum. CONCLUSIONS: The increased levels of APRIL and BAFF in VERA patients suggests that B-cell activation and the development of autoreactive B-cell responses might be crucial in early phases of RA. Therefore, APRIL and BAFF could be promising targets for therapy in the early phase of RA.

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.