Frequency of Deleterious Germline Variants in HER2-Low Breast Cancer Patients Using a Hereditary Multipanel Gene Testing.

HER2-Low is defined as low levels of HER2 expression, based on a score of 1+ on immunohistochemical (IHC) assay or as an IHC score of 2+ and negative results on in situ hybridization (ISH or FISH). They are a heterogeneous population of breast cancers that vary in prognosis and sensitivity to systemic treatments. The frequency and clinical characteristics of pathogenic germline variants (PGVs) in HER2-Low breast cancer (BC) patients is not defined. We analyzed results from patients with BC who underwent multi-gene panel testing (MGPT) (maximum 145 genes) between 2018-2019. We reclassified HER-2 status accordingly. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Of a total of 167 BC patients who underwent MGPT, half were hormone-receptor-positive. The median age was 45 years. About two thirds of the patients were in the earlier stage of BC. A total of 57% of the cases were reclassified as HER-2-negative or -Low. PGVs were found in 19% of the patients overall, as follows: seven BRCA1, four BRCA2, two ATM, one ATR, two CFTR, three CHEK2, one FANCA, one MERTK, one MLH1, three MUTYH, one RAD50, three RAD51C, one RECQL4, and two TP53 mutations. In HER2-Low, 26.5% of the patients had PGVs, and in the overall cohort, this was 19.8%. In conclusion, differences in the prevalence of deleterious germline mutations in HER2-Low BC patients compared to non-HER2-Low BC patients were identified. Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.

A breath of fresh air: impact of insect-borne protozoan parasites on the respiratory system.

The protozoan parasites Plasmodium, Leishmania, and Trypanosoma are transmitted by hematophagous insects and cause severe diseases in humans. These infections pose a global threat, particularly in low-resource settings, and are increasingly extending beyond the current endemic regions. Tropism of parasites is crucial for their development, and recent studies have revealed colonization of noncanonical tissues, aiding their survival and immune evasion. Despite receiving limited attention, cumulative evidence discloses the respiratory system as a significant interface for host-pathogen interactions, influencing the course of (co)infection and disease onset. Due to its pathophysiological and clinical implications, we emphasize that further research is needed to better understand the involvement of the respiratory system and its potential to improve prevention, diagnosis, treatment, and interruption of the chain of transmission.

Prognostic value of programmed cell death ligand 1 (PD-L1) expression in patients with stage III non-small cell lung cancer under different treatment types: a retrospective study.

OBJECTIVE: Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. METHODS: This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. RESULTS: A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. CONCLUSIONS: PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

Robot-assisted transanal minimally invasive surgery for the treatment of rectal adenocarcinoma.

This is a video vignette of a 57-year-old asymptomatic female patient. The patient underwent a screening colonoscopy which revealed a 10 mm scar in the rectum. Biopsy resulted in a well-differentiated tubular adenocarcinoma. Computed tomography and pelvic magnetic resonance imaging confirmed tumor characteristics without distant or lymph nodal metastasis. A minimally invasive robotic transanal resection using the Da Vinci Xi platform was performed, achieving full-thickness lesion excision with uneventful recovery. Histopathology revealed intramucosal adenocarcinoma with free margins. Local resection is advocated for selected T1 lesions and demands a thorough preoperative assessment. Robotic-assisted surgery presents a valuable alternative for early rectal adenocarcinoma management.

Intracorporeal anastomosis could be associated with a higher lymph node yield in right colon cancer surgery: Results of the ICA-LATAM study, a retrospective, multicentre, comparative analysis in Latin America.

AIM: The aim of this work was to compare lymph node (LN) yield in patients operated on for right colon cancer (RCC) using a laparoscopic approach between those receiving an intracorporeal (ICA) or extracorporeal anastomosis (ECA). METHOD: This is a retrospective multicentre study involving patients operated on for RCC in nine tertiary referral centres in Latin America during a 2-year period. The main comparative outcome between groups was the number of LNs harvested between groups. RESULTS: The study included 416 patients, 261 (62.7%) in the ECA group and 155 (37.3%) in the ICA group. Patients in the ECA group were elderly (66 vs. 61 years, p < 0.001). Patients receiving an ICA achieved a significantly higher LN yield than those receiving an ECA (24 vs. 18, p < 0.001). This group also had a lower percentage of patients achieving a substandard LN yield (<12 LNs) (10% vs. 24.8%, p = 0.001) and more patients achieving a high number of harvested LNs (>32 LNs) (15.5% vs. 8.3%, p = 0.039). In the multivariate analysis, ICA was independently related to the primary outcome (LN yield) (OR 3.28, p = 0.027, 95% CI 1.14-9.38). CONCLUSION: In this retrospective study, patients operated on for RCC who received an ICA achieved a higher LN yield. Further studies are needed to reconfirm these findings, and also to find an explanation for these results.

Risk Factors for Early Lower Limb Re-Amputation in Vascular Diseases.

BACKGROUND: Numerous risk factors for lower limb amputations are known; however, this study aimed to identify risk factors for re-amputation in patients within 6 months from an initial lower limb amputation procedure. METHODS: This single-center retrospective cohort study was performed at the Hospital Regional Hans Dieter Schmidt in Brazil. The study included patients who were aged at least 18 years and had undergone lower limb amputation between 2013 and 2022. Patients who died while hospitalized and patients who were lost to follow-up after hospital discharge were excluded from the study. Patient age, sex, number of amputations, revision time, comorbidities, and potential risk factors were extracted from the physical therapy service database and electronic medical records of the hospital. Chi-squared test and student's t-test were used to identify statistical significance. RESULTS: A total of 652 patients were included, of which 35.2% (230) patients underwent re-amputation within 6 months of the first operation. We found that dialysis (P = 0.004; odds ratio [OR] 8.36, 95% confidence interval [CI] 3.09-20.5), smoking (P = 0.004; OR 1.67, 95% CI 1.18-2.35), and hypertension (P = 0.02; OR 1.55, 95% CI 1.09-2.19) were predictive factors for re-amputation within 6 months of lower limb amputation. CONCLUSIONS: Therefore, it is important to intervene early and provide additional support to patients undergoing lower limb amputation with these risk factors to reduce the potential for re-amputation in the future.

Does Tri-Staple™ technology reduce the risk of anastomotic leakage in colorectal surgery? A propensity score matching analysis.

BACKGROUND AND OBJECTIVES: This study evaluates the Tri-Staple™ technology in colorectal anastomosis. METHODS: Patients who underwent rectosigmoidectomy between 2016 and 2022 were retrospectively evaluated and divided into two groups: EEA™ (EEA) or Tri-Staple™ (Tri-EEA). The groups were matched for age, sex, American Society of Anesthesiologists (ASA), and neoadjuvant radiotherapy using propensity score matching (PSM). RESULT: Three hundred and thirty-six patients were included (228 EEA; 108 Tri-EEA). The groups were similar in sex, age, and neoadjuvant therapy. The Tri-EEA group had fewer patients with ASA III/IV scores (7% vs. 33%; p < 0.001). The Tri-EEA group had a lower incidence of leakage (4% vs. 11%; p = 0.023), reoperations (4% vs. 12%; p = 0.016), and severe complications (6% vs. 14%; p = 0.026). There was no difference in complications, mortality, readmission, and length of stay. After PSM, 108 patients in the EEA group were compared with 108 in the Tri-EEA group. The covariates sex, age, neoadjuvant radiotherapy, and ASA were balanced, and the risk of leakage (4% vs. 12%; p = 0.04), reoperation (4% vs. 14%; p = 0.014), and severe complications (6% vs. 15%; p = 0.041) remained lower in the Tri-EEA group. CONCLUSION: Tri-Staple™ reduces the risk of leakage in colorectal anastomosis. However, this study provides only insights, and further research is warranted to confirm these findings.

Surgical and medical outcomes in robotic compared to laparoscopic colectomy global prospective cohort from the American college of surgeons national surgical quality improvement program.

BACKGROUND: Evidence regarding the outcomes benefits of robotic approach, when compared to a laparoscopic approach, in colectomy remain limited. OBJECTIVE: This study aimed to analyze the value of robotic approach compared to laparoscopic approach in minimally invasive colectomy. DESIGN: Cohort study of the National Surgical Quality Improvement Program (NSQIP). SETTING: This study included data from the NSQIP from 1/2016 to 12/2021. PATIENT: Adult patients undergoing minimally invasive (laparoscopic or robotic) colorectal surgery. INTERVENTION: Robotic versus laparoscopic colectomy. OUTCOME MEASURES: Risk ratios for the incidence of medical and surgical morbidity and overall mortality. RESULTS: Compared to laparoscopic, robotic colectomy was associated with a significant decrease in postoperative morbidity [RR 0.84 (95%CI 0.72-0.96), P < 0.001], a significant reduction in postoperative mortality [RR 0.83 (95%CI 0.79-0.90), P 0.010)], and in post operative ileus [RR: 0.80 (95%CI 0.75-0.84), P < 0.001]. Yet, robotic approach was associated with a significant increase in total operative time despite a significant decrease in total length of stay. No benefit was observed regarding anastomotic leak. LIMITATIONS: Observational nature of the study cannot exclude residual bias. CONCLUSIONS: In this prospective cohort from the NSQIP, robotic colectomy was associated with a significant reduction in postoperative ileus, unplanned conversion to open surgery, morbidity, and overall mortality when compared to laparoscopic colectomy.

Bowel preparation for elective colectomy in Crohn's disease: results from a global cohort study using the NSQIP database.

AIM: The role of bowel preparation before colectomy in Crohn's disease patients remains controversial. This retrospective analysis of a prospective cohort study aimed to investigate the clinical outcomes associated with mechanical and antibiotic colon preparation in patients diagnosed with Crohn's disease undergoing elective colectomy. METHOD: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program participant user files from 2016 to 2021. A total of 6244 patients with Crohn's disease who underwent elective colectomy were included. The patients were categorized into two groups: those who received combined colon preparation (mechanical and antibiotic) and those who did not receive any form of bowel preparation. The primary outcomes assessed were the rate of anastomotic leak and the occurrence of deep organ infection. Secondary outcomes included all-cause short-term mortality, clinical-related morbidity, ostomy creation, unplanned reoperation, operative time, hospital length of stay and ileus. RESULTS: Combined colon preparation was associated with significantly reduced risks of anastomotic leak (relative risk 0.73, 95% CI 0.56-0.95, P = 0.021) and deep organ infection (relative risk 0.68, 95% CI 0.56-0.83, P < 0.001). Additionally, patients who underwent colon preparation had lower rates of ostomy creation, shorter hospital stays and a decreased incidence of ileus. However, there was no significant difference in all-cause short-term mortality or the need for unplanned reoperation between the two groups. CONCLUSION: This study shows that mechanical and antibiotic colon preparation may have clinical benefits for patients with Crohn's disease undergoing elective colectomy.

Prognostic value of programmed cell death ligand 1 (PD-L1) expression in patients with stage III non-small cell lung cancer under different treatment types: a retrospective study

ABSTRACT Objective Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. Methods This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. Results A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. Conclusions PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.

Mesh repair versus non-mesh repair for incarcerated and strangulated groin hernia: an updated systematic review and meta-analysis.

BACKGROUND: Mesh repair in incarcerated or strangulated groin hernia is controversial, especially when bowel resection is required. We aimed to perform a meta-analysis comparing mesh and non-mesh repair in patients undergoing emergency groin hernia repair. METHODS: We performed a literature search of databases to identify studies comparing mesh and primary suture repair of patients with incarcerated or strangulated inguinal or femoral hernias who underwent emergency surgery. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics. RESULTS: 1095 studies were screened and 101 were thoroughly reviewed. Twenty observational studies and four randomized controlled trials comprising 12,402 patients were included. We found that mesh-based repair had reduced recurrence (OR 0.36; 95% CI 0.19, 0.67; P = 0.001; I2 = 35%), length of hospital stay (OR - 1.02; 95% CI - 1.87, - 0.17; P = 0.02; I2 = 94%) and operative time (OR - 9.21; 95% CI - 16.82, - 1.61; P = 0.02; I2 = 95%) without increasing surgical site infection, mortality or postoperative complications such as seroma, chronic, ileus or urinary retention. In the subgroup analysis of patients that underwent bowel resection, we found that mesh repair was associated with an increased risk of surgical site infection (OR 1.74; 95% CI 1.04, 2.91; P = 0.04; I2 = 9%). CONCLUSIONS: Mesh repair for incarcerated and strangulated groin hernias reduces recurrence without an increase in postoperative complications and should be considered in clean cases. However, in the setting of bowel resection, mesh repair might increase the incidence of surgical site infection.

Production of Recombinant Zika Virus Envelope Protein by Airlift Bioreactor as a New Subunit Vaccine Platform.

The Zika Virus (ZIKV) is an emerging arbovirus of great public health concern, particularly in the Americas after its last outbreak in 2015. There are still major challenges regarding disease control, and there is no ZIKV vaccine currently approved for human use. Among many different vaccine platforms currently under study, the recombinant envelope protein from Zika Virus (rEZIKV) constitutes an alternative option for vaccine development and has great potential for monitoring ZIKV infection and antibody response. This study describes a method to obtain a bioactive and functional rEZIKV using an E. coli expression system, with the aid of a 5-L airlift bioreactor and following an automated fast protein liquid chromatography (FPLC) protocol, capable of obtaining high yields of approximately 20 mg of recombinant protein per liter of bacterium cultures. The purified rEZIKV presented preserved antigenicity and immunogenicity. Our results show that the use of an airlift bioreactor for the production of rEZIKV is ideal for establishing protocols and further research on ZIKV vaccines bioprocess, representing a promising system for the production of a ZIKV envelope recombinant protein-based vaccine candidate.

An Overview of Robotic Colorectal Surgery Adoption and Training in Brazil.

Background and Objectives: Robotic surgical systems have rapidly become integrated into colorectal surgery practice in recent years, particularly for rectal resections, where the advantages of robotic platforms over conventional laparoscopy are more pronounced. However, as with any technological advancement, the initial high costs can be a limiting factor, leading to unequal health service access, especially in middle- and lower-income countries. Materials and Method: A narrative review was conducted with the objective of providing an overview of the escalating adoption, current training programmes, and certification process of robotic colorectal surgery in Brazil. Results: Brazil has witnessed a rapid increase in robotic platforms in recent years. Currently, there are 106 robotic systems installed nationwide. However, approximately 60% of the medical facilities which adopted robotic platforms are in the Southeast region, which is both the most populous and economically prosperous in the country. The Brazilian Society of Coloproctology recently established clear rules for the training programme and certification of colorectal surgeons in robotic surgery. The key components of the training encompass theoretical content, virtual robotic simulation, observation, assistance, and supervised procedures in colorectal surgery. Although the training parameters are well established, no colorectal surgery residency programme in Brazil has yet integrated the teaching and training of robotic surgery into its curriculum. Thus far, the training process has been led by private institutions and the industry. Conclusion: Despite the fast spread of robotic platforms across Brazil, several challenges still need to be addressed to democratise training and promote the widespread use of these platforms. It is crucial to tackle these obstacles to achieve greater integration of robotic technology in colorectal surgery throughout the country.

Keyhole Versus Sugarbaker Mesh Configuration in Parastomal Hernia Repair: A Systematic Review and Meta-analysis.

BACKGROUND: Parastomal hernia repairs (PHRs) are often complex and challenging, even for experienced abdominal wall surgeons. Although the ideal therapeutic option in the setting of a parastomal hernia is to restore intestinal continuity, this is often not feasible, and numerous techniques have been described for PHR. Current guidelines recommend using mesh for elective PHR, but there is a scarcity of evidence comparing different PHR techniques. We aimed to report a meta-analysis comparing the outcomes of the "Sugarbaker" and "Keyhole" mesh configuration in PHR. METHODS: A literature search of PubMed, Embase, Scopus, and Cochrane Library databases was performed to identify studies comparing Sugarbaker and Keyhole mesh configuration in PHR. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics. RESULTS: A total of 3247 studies were screened, and 27 were fully reviewed. Ten studies and 632 patients were included in the meta-analysis. Three hundred five patients (48.3%) with Keyhole and 327 patients (51.7%) with Sugarbaker mesh configuration. Four hundred thirty-three patients (68.5%) underwent laparoscopic PHR with intraperitoneal onlay mesh. Sugarbaker mesh configuration was associated with lower hernia recurrence compared with Keyhole (odds ratio: 0.39; 95% CI: 0.19-0.83; P = 0.01; I2 = 46%). No differences were seen in overall complications, reoperations, stoma outlet obstruction, mesh infection, and postoperative bleeding. CONCLUSION: PHR with Sugarbaker mesh configuration is associated with decreased hernia recurrence compared with Keyhole and had similar rates of overall complications, reoperations, stoma outlet obstruction, mesh infection, and postoperative bleeding.