Hydroalcoholic extract of Araucaria sp. brown propolis alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration and oxidative damage.

OBJECTIVE: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. KEY FINDINGS: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. CONCLUSION: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.

Tagetes erecta L.: A traditional medicine effective in inflammatory process treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Tagetes erecta L. (Asteraceae), popularly known as Aztec Marigold, is used in folk medicine to treat several ailments including inflammatory processes. Despite its historical use, the specific mechanisms through which it may modulate inflammation, particularly its effects on neutrophils and macrophages activation, have not yet been completely investigated. AIM OF THE STUDY: This study aimed to elucidate the anti-inflammatory mechanism of the hydroalcoholic extract obtained from T. erecta flowers, focusing on its role in the regulation of neutrophil and macrophage functions. MATERIAL AND METHODS: The production of TNF, IL-6, CXCL-1, IL-1ß, IL-10 (ELISA) and NO (Griess reaction), adhesion molecule expression (CD62L, CD49d and CD18, flow cytometry), and chemotaxis were analyzed in vitro using oyster glycogen-recruited peritoneal neutrophils or macrophages (RAW 264.7) stimulated with lipopolysaccharide (LPS) and treated with the extract (1, 10 or 100 µg/mL). The resolution of inflammation was accessed by efferocytosis assay. The in vivo anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally treated with the T. erecta extract (30, 100 or 300 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (TNF, IL-6 and IL-1ß, ELISA) and protein exudation (Bradford reaction) were quantified in the inflamed exudate. RESULTS: In vitro studies demonstrated that the extract inhibited neutrophil chemotaxis and reduced the production and/or release of cytokines (TNF, IL-1ß, CXCL1, and IL-6) as well as nitric oxide (NO) by neutrophils and macrophages when stimulated with LPS. Neutrophils treated with LPS and incubated with the extract showed an increase in CD62L expression, which leads to the impairment of neutrophil adhesion. The extract also enhanced efferocytosis of apoptotic neutrophils by macrophages, which was accompanied by increased IL-10 secretion and decreased TNF levels. In vivo studies yielded similar results, showing reduction in neutrophil migration, protein exudation, and cytokine release (TNF, IL-6, and IL-1ß). CONCLUSIONS: Together, the data herein obtained shows that T. erecta flower extract has anti-inflammatory effects by regulating inflammatory mediators, limiting neutrophil migration, and promoting efferocytosis. The in vivo results suggest that an herbal medicine made with T. erecta could represent an interesting pharmacological tool for the treatment of acute inflammatory condition.

Metabolic and Bariatric Surgery in Patients with Obesity Class V (BMI > 60 kg/m2): a Modified Delphi Study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the preferred method to achieve significant weight loss in patients with Obesity Class V (BMI > 60 kg/m2). However, there is no consensus regarding the best procedure(s) for this population. Additionally, these patients will likely have a higher risk of complications and mortality. The aim of this study was to achieve a consensus among a global panel of expert bariatric surgeons using a modified Delphi methodology. METHODS: A total of 36 recognized opinion-makers and highly experienced metabolic and bariatric surgeons participated in the present Delphi consensus. 81 statements on preoperative management, selection of the procedure, perioperative management, weight loss parameters, follow-up, and metabolic outcomes were voted on in two rounds. A consensus was considered reached when an agreement of ≥ 70% of experts' votes was achieved. RESULTS: A total of 54 out of 81 statements reached consensus. Remarkably, more than 90% of the experts agreed that patients should be notified of the greater risk of complications, the possibility of modifications to the surgical procedure, and the early start of chemical thromboprophylaxis. Regarding the choice of the procedure, SADI-S, RYGB, and OAGB were the top 3 preferred operations. However, no consensus was reached on the limb length in these operations. CONCLUSION: This study represents the first attempt to reach consensus on the choice of procedures as well as perioperative management in patients with obesity class V. Although overall consensus was reached in different areas, more research is needed to better serve this high-risk population.

Global benchmarks in primary robotic bariatric surgery redefine quality standards for Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND: Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS: Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50 kg/m2, or age greater than 65 years. RESULTS: A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42 min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION: The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer.

The impact of antinuclear antibodies seroconversion induced by anti-tumor necrosis factor α agents on the clinical outcomes in rheumatic patients.

INTRODUCTION: Anti-tumor necrosis factor α (anti-TNFα) agents can potentially induce the anti-nuclear antibodies (ANA) development over time. Evidence of the real impact of these autoantibodies on clinical response to treatment in rheumatic patients is still scarce. OBJECTIVES: To explore the impact of ANA seroconversion induced by anti-TNFα therapy on clinical outcomes in biologic-naïve patients with Rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: An observational retrospective cohort study enrolling biologic-naïve patients with RA, axSpA and PsA who started their first anti-TNFα agent was conducted for 24 months(M). Sociodemographic data, laboratory findings, disease activity and physical function scores were collected at baseline, 12M and 24M. To examine the differences between the groups with and without ANA seroconversion, independent samples t-tests, Mann-Whitney U-tests and chi-square tests were performed. Linear and logistic regression models were used to assess the effects of ANA seroconversion on the clinical response to treatment. RESULTS: A total of 432 patients with RA (N=185), axSpA (N=171) and PsA (N=66) were included. ANA seroconversion rate at 24M was 34.6%, 64.3% and 63.6% for RA, axSpA and PsA, respectively. Regarding sociodemographic and clinical data in RA and PsA patients, no statistically significant differences between groups with and without ANA seroconversion were found. In axSpA patients, ANA seroconversion was more frequent in patients with higher body mass index (p=0.017) and significantly less frequent in patients treated with etanercept (p=0.01). Regarding disease activity, DAS28 for RA patients and ASDAS-CRP for axSpA patients were significantly higher in ANA seroconversion group at 12M (p=0.017 and p=0.009, respectively). For PsA patients, CDAI was significantly higher in ANA seroconversion group at 24M (p=0.043). Overall switching rate of biologic disease-modifying antirheumatic drugs (bDMARD) was significantly higher in the ANA seroconversion group over time (p=0.025). For RA patients, ANA seroconversion predicted DAS28 (ß=-0.21, 95%CI[-1.86;-0.18], p=0.017) at 12M. CONCLUSIONS: ANA seroconversion induced by anti-TNFα agents could interfere in clinical response of patients with rheumatic diseases. The presence of these autoantibodies can be considered as a potential predictor of poor treatment response and higher need for bDMARD switching over time.

The impact of Hafnia alvei HA4597™ on weight loss and glycaemic control after bariatric surgery - study protocol for a triple-blinded, blocked randomized, 12-month, parallel-group, placebo-controlled clinical trial.

BACKGROUND: Subjects with obesity exhibit changes in gut microbiota composition and function (i.e. dysbiosis) that contribute to metabolic dysfunction, including appetite impairment. Although bariatric surgery is an effective treatment for obesity with a great impact on weight loss, some subjects show weight regain due to increased energy intake after the surgery. This surgery involves gut microbiota changes that promote appetite control, but it seems insufficient to completely restore the obesity-associated dysbiosis - a possible contributor for weight regain. Thus, modulating gut microbiota with probiotics that could improve appetite regulation as a complementary approach to post-operative diet (i.e. Hafnia alvei HA4597™), may accentuate post-surgery weight loss and insulin sensitivity. METHODS: This is a protocol of a triple-blinded, blocked-randomized, parallel-group, placebo-controlled clinical trial designed to determine the effect of Hafnia alvei HA4597™ supplementation on weight loss and glycaemic control 1 year after bariatric surgery. Patients of Hospital CUF Tejo, Lisbon, that undergo Roux-en-Y gastric bypass are invited to participate in this study. Men and women between 18 and 65 years old, with a BMI ≥ 35 kg/m2 and at least one severe obesity-related comorbidity, or with a BMI ≥ 40 kg/m2, and who are willing to take 2 capsules of Hafnia alvei HA4597™ probiotic supplements (equivalent to 5 × 107 CFU) vs. placebo per day for 90 days are included in this study. Assessments are carried out at baseline, 3, 6, 9, and 12 months after the surgery. Loss of weight in excess and glycated haemoglobin are considered primary outcomes. In addition, changes in other metabolic and inflammatory outcomes, gut microbiota composition and metabolites, as well as gastrointestinal quality of life are also being assessed during the trial. DISCUSSION: The evidence obtained in this study will provide relevant information regarding the profile of the intestinal microbiota of individuals with severe obesity and the identification of the risk/benefit ratio of the use of Hafnia alvei HA4597™ as an adjunctive treatment in the maintenance of metabolic and weight control one year after the surgical intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05170867. Registered on 28 December 2021.

Prognosis of patients with acute lymphoblastic leukaemia relapsing after allogeneic stem cell transplantation.

The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (allo-SCT) are poor, with few data available in this setting. OBJECTIVE AND METHODS: To evaluate the outcomes of patients with ALL presenting relapsed after allo-SCT, we performed a retrospective study including 132 from 11 centres in Spain. RESULTS: Therapeutic strategies consisted of palliative treatment (n = 22), chemotherapy (n = 82), tyrosine kinase inhibitors (n = 26), immunotherapy with inotuzumab and/or blinatumumab (n = 19), donor lymphocyte infusions (n = 29 pts), second allo-SCT (n = 37) and CAR T therapy (n = 14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95% confidence interval [CI]: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo-SCT, the 5-year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo-SCT, late relapse, 1st complete remission at 1st allo-SCT and chronic graft-versus-host disease confirmed their positive impact on survival in the multivariable analysis. CONCLUSION: Despite the poor prognosis of patients with ALL presenting relapse after a first allo-SCT, some can be satisfactorily rescued and a second allo-SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo-SCT.

Acute kidney injury after allogeneic hematopoietic stem cell transplantation - Predictors and survival impact: A single center retrospective study.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting. PATIENTS AND METHODS: We performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019. RESULTS: AKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p=0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p=0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p<0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p=0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p=0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p=0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p=0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p=0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p=0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival. CONCLUSION: Patients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.

Brown-Séquard syndrome in a patient with spondyloarthritis after COVID-19 vaccine: a challenging differential diagnosis.

A 41-year-old woman with pre-radiographic axial and peripheric spondyloarthritis, taking adalimumab since 2010, started motor impairment of the right limbs and numbness of the left leg seven days after the administration of COVID-19 mRNA vaccine. Adalimumab was taken 47 days before clinical onset. A comprehensive study for infectious, autoimmune and neoplastic causes were unremarkable. MRI depicted an acute inflammatory lesion at C2 level with gadolinium enhancement. The patient started methylprednisolone with clinical improvement. Three scenarios should be considered: primary CNS inflammatory disorder or a secondary manifestation of the underlying rheumatologic disease; immune-mediated inflammatory lesion triggered by vaccine; demyelinating event due to adalimumab.

Involvement of a neutrophil-mast cell axis in the effects of Piper malacophyllum (C. PESL) C. DC extract and its isolated compounds in a mouse model of dysmenorrhoea.

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6-8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour.

Allogeneic stem cell transplant in relapsed/ refractory Hodgkin lymphoma: A 21 years' experience.

Background: Allogenic stem cell transplant (alloSCT) has been used for several decades as a salvage strategy for relapsed/ refractory Hodgkin lymphoma (R/R HL), being a durable disease control method for some patients. Methods: A unicenter retrospective analysis was performed about alloSCT in R/R HL along 21 years. A survival analysis was made in search for prognostic factors with impact in overall survival (OS)/progression free survival (PFS). Results: Thirty-five patients were reviewed: median age 30years [17-46], 57.1% males, 82.9% had an esclero-nodular HL, 54.3% were in stage II of disease, and 42.9% achieved a complete response before the alloSCT. The donor type was matched-related in 54.3% and the stem cell source was peripheral blood in 97.1% of the grafts. All patients did a reduced intensity conditioning regimen. The overall response rate was 85.7% (complete in 68.6%, partial in 17.1%). Acute graft versus host disease grade II-IVwas seen in 45.7%. Transplant related mortality at day 360 was 17.9%. The median OS was 61 months (95% confidente interval: 33.6-88.3). The median PFS was 1Omonths (95% confidente interval: 3.1-16.9). Patients with >3Oyears at the alloSCT time and a previous autologous SCT showed better OS/PFS in the univariate analysis; having a matched donor and absence of infections along the alloSCT also improved PFS. Conclusions: AlloSCT is a feasible procedure in patients with R/R HL, being able to stabilize the disease in a large number of patients. However, it has a relevant toxicity in patients highly pre-treated.

Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial.

BACKGROUND: Acute graft-versus-host disease (GVHD) is a common and life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT); there is an urgent unmet need for effective therapies. We aimed to evaluate the Janus kinase 1 inhibitor itacitinib versus placebo, both in combination with corticosteroids, for initial treatment of acute GVHD. METHODS: GRAVITAS-301 was an international, double-blind, adaptive (group sequential design) phase 3 study conducted at 129 hospitals and community practices in 19 countries. Eligible patients were aged 18 years or older, had previously received allogeneic HSCT for a haematological malignancy, developed grades II-IV acute GVHD, and received up to 2 days of systemic corticosteroids. Patients were stratified by clinical standard-risk or high-risk acute GVHD and randomly assigned (1:1), via a centralised interactive voice response system, to receive either oral itacitinib (200 mg) or placebo once daily, both in addition to corticosteroids. The primary endpoint was overall response rate (ORR) at day 28 (defined as the proportion of patients with complete response, very good partial response, or partial response 28 days after the start of treatment). For sample size determination, an absolute improvement in ORR at day 28 over standard therapy of 16% was considered clinically meaningful. Efficacy analyses were performed in the intention-to-treat population; safety analyses included patients who received at least one dose of study drug. GRAVITAS-301 is registered with ClinicalTrials.gov (NCT03139604) and is complete. FINDINGS: Between July 19, 2017, and Oct 3, 2019, 439 patients were randomly assigned to receive either itacitinib plus corticosteroids (n=219; itacitinib group) or placebo plus corticosteroids (n=220; placebo group). 173 (39%) patients were female and 390 (89%) were White. At baseline, 107 (24%) of 439 patients (itacitinib 51 [23%] of 219; placebo 56 [25%] of 220) had clinical high-risk acute GVHD. The ORR at day 28 was 74% (95% CI 67·6-79·7; 162 of 219; complete response 53% [116 of 219]) for itacitinib and 66% (59·7-72·6; 146 of 220; complete response, 40% [89 of 220]) for placebo (odds ratio for ORR 1·45, 95% CI 0·96-2·20; two-sided p=0·078). Grade 3 or worse adverse events occurred in 185 (86%) of 215 itacitinib recipients and 178 (82%) of 216 placebo recipients, and most commonly included thrombocytopenia or platelet count decreased (78 [36%] vs 68 [31%]), neutropenia or neutrophil count decreased (49 [23%] vs 45 [21%]), anaemia (42 [20%] vs 26 [12%]), and hyperglycaemia (26 [12%] vs 28 [13%]). Treatment-related deaths occurred in three of 215 patients (1%) in the itacitinib group and four of 216 (2%) in the placebo group. INTERPRETATION: The observed improvement in ORR at day 28 with the addition of itacitinib versus placebo to corticosteroids did not reach the prespecified significance level. Further studies might provide additional insight into the utility of selective JAK1 inhibition for the treatment of acute GVHD. FUNDING: Incyte.

Technical aspects and standardization of the totally robotic Roux-en-Y gastric bypass. Results of a single surgeon experience with a 5-year follow-up.

INTRODUCTION: The use of robotics in bariatric surgery is increasing worldwide, with as main objective reducing complications and optimising surgical outcome. This study presents the results of a single surgeon 8-year experience with a totally robotic Roux-en-Y gastric bypass (RYGB). METHODS: A total of 183 consecutive patients underwent a robotic bariatric procedure. A retrospective analysis was performed of all patient files to obtain patient characteristics, weight loss results and per- and postoperative morbidity. For long-term follow-up all patients were contacted one by one. RESULTS: In 155/183 patients, a primary RYGB was performed, 23 procedures were revisional cases and in 5 other procedures were performed. Mean initial weight was 112.07 (±20.5) kg, mean start BMI was 40.8 (±5.36) kg/m2. There were no conversions and no major intraoperative complications. In the early postoperative period we note two revisions; one postoperative bleeding and one missed iatrogenic enterotomy. Mean length of stay in the hospital was 3.50 (±1.20) days. After a mean follow-up of 62.06 (±32.76) months, mean BMI was 28.07 (±4.88) kg/m2 with an % excess body mass index loss of 84.02 (±31.64) %. Patient satisfaction was high, with 95.1% of the patients being happy. The main complaint in the remaining patients was weight regain. CONCLUSION: The robotic RYGB is a safe and reproducible approach to treat morbid obesity. A secure hand-sewn gastrojejunal anastomosis, quick recovery and better ergonomics are the main advantages of this technique.

Pancreatic Cancer and Primary Sjögren's Syndrome: A Case Report.

Primary Sjögren syndrome (SS) is a chronic inflammatory systemic autoimmune disease with a high risk of malignancy development, namely, lymphoproliferative neoplasms. Few studies also reported a high risk of solid cancers; however, the coexistence of primary SS and pancreatic cancer has been rarely described. In this paper, we aim to describe a case of a 59-year-old woman who was an active smoker with sicca symptoms and symmetrical polyarthritis and was diagnosed with primary SS two years before the development of metastatic pancreatic adenocarcinoma. Despite institution of chemotherapy, the patient succumbed to the malignancy. Besides that, we explore the link between primary SS and solid cancers including the main predictors of malignancy and the role of primary SS as a paraneoplastic syndrome. Patients with primary SS should be closely monitored for malignancy, not only for hematological cancer, but also for solid tumors. Further research is necessary to understand which are the predictors of cancer proliferation in primary SS patients.

Confinement During the COVID-19 Pandemic After Metabolic and Bariatric Surgery-Associations Between Emotional Distress, Energy-Dense Foods, and Body Mass Index.

PURPOSE: To estimate the association of emotional distress with both consumption of energy-dense micronutrient-poor foods (EDF) and body mass index (BMI) and the association between EDF consumption and change in BMI, during COVID-19 pandemic in patients with prior bariatric surgery. MATERIALS AND METHODS: This cross-sectional study applied an online structured questionnaire to 75 postoperative bariatric patients during the first Portuguese lockdown. Emotional distress was assessed trough the Hospital Anxiety and Depression Scale (HADS) and dietary intake was evaluated by Food Frequency Questionnaire (FFQ). Self-reported BMI prior to and at the end of confinement was used to compute BMI change. Pre-surgery BMI was computed from measured height and weight from clinical records. RESULTS: After adjustment for education, sex, time since surgery, pre-surgery BMI, and exercise practice, moderate/severe scores in HADS were significantly positively associated with consumption of EDF (ẞ = 0.799; 95% CI: 0.051, 1.546), but not with BMI. Daily EDF consumption significantly increased the odds of maintaining/increasing BMI (OR = 3.34; 95% CI: 1.18, 9.45), instead of decreasing it (reference). Sweets consumption was the only subcategory of EDF significantly positively associated with the odds of a worse outcome in BMI change (OR = 4.01; 95% CI: 1.13, 14.22). CONCLUSIONS: Among postoperative bariatric patients, higher reported levels of emotional distress during confinement are associated with increased EDF consumption. Increased EDF consumption during confinement, particularly sweets, is associated with higher odds of bariatric patients not decreasing their BMI. Additional effort is needed to address inadequate lifestyle behaviors among these patients in the context of the COVID-19 pandemic.

Genetic Variation in PFKFB3 Impairs Antifungal Immunometabolic Responses and Predisposes to Invasive Pulmonary Aspergillosis.

Activation of immune cells in response to fungal infection involves the reprogramming of their cellular metabolism to support antimicrobial effector functions. Although metabolic pathways such as glycolysis are known to represent critical regulatory nodes in antifungal immunity, it remains undetermined whether these are differentially regulated at the interindividual level. In this study, we identify a key role for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the immunometabolic responses to Aspergillus fumigatus. A genetic association study performed in 439 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) and corresponding donors revealed that the donor, but not recipient, rs646564 variant in the PFKFB3 gene increased the risk of invasive pulmonary aspergillosis (IPA) after transplantation. The risk genotype impaired the expression of PFKFB3 by human macrophages in response to fungal infection, which was correlated with a defective activation of glycolysis and the ensuing antifungal effector functions. In patients with IPA, the risk genotype was associated with lower concentrations of cytokines in the bronchoalveolar lavage fluid samples. Collectively, these findings demonstrate the important contribution of genetic variation in PFKFB3 to the risk of IPA in patients undergoing HSCT and support its inclusion in prognostic tools to predict the risk of fungal infection in this clinical setting. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. Activation of glycolysis is essential for innate immune cells to mount effective antifungal responses. In this study, we report the contribution of genetic variation in the key glycolytic activator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) to the risk of invasive pulmonary aspergillosis (IPA) after allogeneic hematopoietic stem cell transplantation. The PFKFB3 genotype associated with increased risk of infection was correlated with an impairment of the antifungal effector functions of macrophages in vitro and in patients with IPA. This work highlights the clinical relevance of genetic variation in PFKFB3 to the risk of IPA and supports its integration in risk stratification and preemptive measures for patients at high risk of IPA.

The First Modified Delphi Consensus Statement for Resuming Bariatric and Metabolic Surgery in the COVID-19 Times.

The purpose of this study was to achieve consensus amongst a global panel of expert bariatric surgeons on various aspects of resuming Bariatric and Metabolic Surgery (BMS) during the Coronavirus Disease-2019 (COVID-19) pandemic. A modified Delphi consensus-building protocol was used to build consensus amongst 44 globally recognised bariatric surgeons. The experts were asked to either agree or disagree with 111 statements they collectively proposed over two separate rounds. An agreement amongst ≥ 70.0% of experts was construed as consensus as per the predetermined methodology. We present here 38 of our key recommendations. This first global consensus statement on the resumption of BMS can provide a framework for multidisciplinary BMS teams planning to resume local services as well as guide future research in this area.

Entre chegadas e partidas: conversas intergeracionais no Projeto de Extensão Saúde do Idoso / Between arrivals and departures: intergenerational conversation in the Elderly Health Extension Project

A considerar a complexidade da formação médica atual e da compreensão multifatorial do envelhecimento, surgiu o Projeto de Extensão Saúde do Idoso (PES I), uma extensão universitária que buscou sensibilizar os estudantes de medicina sobre as diferentes dimensões da velhice a partir de encontros com idosos em uma Instituição de Longa Permanência (ILPI), promovendo o intercâmbio de saberes. Este artigo apresenta uma pesquisa qualitativa realizada a partir da análise de narravas elaboradas pelos extensionistas ao final de sua participação no PESI, com foco nas experiências e aprendizados construídos a partir delas. Foi realizada análise temática de conteúdo dos materiais dialogando com referenciais teóricos das ciências sociais e da comunicação em saúde, com resultados apresentados em quatro categorias: as chegadas, as diferentes velhices, as conversas e as pardas. As chegadas de extensionistas e idosos ao Lar discorrem sobre as novas vivências e desafios neste novo cenário; As diferentes velhices são discutidas na segunda categoria, trazendo compreensões e ressignificações; As conversas e outras formas de comunicação são trazidas numa categoria que foca na interação dos atores do processo; Finalizamos os resultados refletindo sobre as percepções de perdas, interrupções, despedidas e terminalidade. Concluímos, através da análise das experiências narradas, que o PESI sensibilizou os estudantes de Medicina para as questões da velhice institucionalizada. Promoveu o convívio intergeracional e a construção de saberes entre a academia e a comunidade. Propiciou uma percepção ampliada da velhice e superação dos estereótipos sobre ILPIs. As análises indicam que os aprendizados repercutiram na formação dos futuros profissionais de saúde.

Considering the complexity of current medical training and the multifactorial understanding of aging, the Elderly Health Extension Project (PESI), a university extension that sought to sensitize medical students about the different dimensions of old age came from meetings with elderly people in a Home for the Aged, promoting the exchange of knowledges. This article presents a qualitative research based on the analysis of narratives elaborated by the extension agents at the end of their participation in PESI, focusing on the experiences and learning built from them. A thematic analysis of the content of the materials was carried out in dialogue with theoretical references of the social sciences and health communication, with results presented in four categories: arrivals, different old age, conversations and departures. The arrivals of extension agents and old ages to the Home discuss new experiences and challenges in this new scenario; The different old age are discussed in the second category, bringing understandings and resignifications; Conversations and other forms of communication are brought into a category that focuses on the interaction of process actors; We finish the results reflecting on the perceptions of losses, interruptions, farewells and termination. We conclude that the PESI sensitized medical students to issues of institutionalized old age. It promoted the intergenerational conviviality and the construction of knowledge between the academy and the community. It provided an expanded perception of old age and overcoming stereotypes about ILPIs. The analyzes indicate that the learning has had repercussions on the medical training of the students.

Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplant.

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Romiplostim and eltrombopag are the currently available thrombopoietin receptor agonists (TPO-RAs), and some studies with very small numbers of cases have reported their potential efficacy in the allo-SCT setting. The present retrospective study evaluated the safety and efficacy of TPO-RAs in 86 patients with persistent thrombocytopenia after allo-HSCT. Sixteen patients (19%) had isolated thrombocytopenia (PT), and 71 (82%) had secondary failure of platelet recovery (SFPR). TPO-RA therapy was started at a median of 127 days (range, 27 to 1177 days) after allo-SCT. The median initial and maximum administered doses were 50 mg/day (range, 25 to 150 mg/day) and 75 mg/day (range, 25 to 150 mg/day), respectively, for eltrombopag and 1 µg/kg (range, 1 to 7 µg/kg) and 5 µg/kg (range, 1 to 10 µg/kg), respectively, for romiplostin. The median platelet count before initiation of TPO-RA therapy was 14,000/µL (range, 1000 to 57,000/µL). Platelet recovery to ≥50,000/µL without transfusion support was achieved in 72% of patients at a median time of 66 days (range, 2 to 247 days). Eighty-one percent of the patients had a decreased number of megakaryocytes before treatment, showing a slower response to therapy (P = .011). The median duration of treatment was 62 days (range, 7 to 700 days). Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the patients. At last follow-up, 81% of patients had discontinued TPO-RAs and maintained response, and 71% were alive. To our knowledge, this is the largest series analyzing the use of TPO-RAs after allo-SCT reported to date. Our results support the efficacy and safety in this new setting. Further prospective trials are needed to increase the level of evidence and to identify predictors of response.