Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1–2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial

Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1–2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). Conclusions: The 3-year survival and relapse rates of T1–2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Probing the Effects of Local Frustration in the Folding of a Multidomain Protein

Our current knowledge of protein folding is primarily based on experimental data obtained from isolated domains. In fact, because of their complexity, multidomain proteins have been elusive to the experimental characterization. Thus, the folding of a domain in isolation is generally assumed to resemble what should be observed for more complex structural architectures. Here we compared the folding mechanism of a protein domain in isolation and in the context of its supramodular multidomain structure. By carrying out an extensive mutational analysis we illustrate that while the early events of folding are malleable and influenced by the absence/presence of the neighboring structures, the late events appear to be more robust. These effects may be explained by analyzing the local frustration patterns of the domain, providing critical support for the funneled energy landscape theory of protein folding, and highlighting the role of protein frustration in sculpting the early events of the reaction

Cholecystectomy in situs viscerum inversus totalis. Does laparoscopy increase the pitalls?

Situs viscerum inversus is a rare condition in which the organs are transposed, totally or partially, to the opposite side of the body. Normally, there are no organ dysfunctions. Clinically, symptoms of cholelithiasis may be clear but confused by the location of the gallbladder on the opposite side. We report the case of a 43-year-old female with occasional colic pain in the epigastrium radiating to the right side and subscapular region, particularly after lunch. The laboratory findings showed normal values and, at physical examination, deep palpation of the abdomen in the epigastric region provoked pain. X-rays, ultrasonography, and CT scan showed the presence of multiple gallstones and the situs viscerum inversus of the abdominal organs. The only pathological finding was cholecystolithiasis. Laparoscopic cholecystectomy was judged advisable. Situs viscerum inversus is not a contraindication for laparoscopic cholecystectomy. This abnormal anatomical condition may create some initial difficulty for the surgeons, because of the inverted position of the organs. The peculiarity of our case is the unlikely site of the abdominal pain, located in the epigastrium and on the right side although the patient had situs viscerum inversus. Laparoscopic cholecystectomy can be performed on the left-sided gallbladder proceeding with the "american technique". In difficult cases, open cholecystectomy can be unavoidable.Situs viscerum inversus is a rare condition in which the organs are transposed, totally or partially, to the opposite side of the body. Normally, there are no organ dysfunctions. Clinically, symptoms of cholelithiasis may be clear but confused by the location of the gallbladder on the opposite side. We report the case of a 43-year-old female with occasional colic pain in the epigastrium radiating to the right side and subscapular region, particularly after lunch. The laboratory findings showed normal values and, at physical examination, deep palpation of the abdomen in the epigastric region provoked pain. X-rays, ultrasonography, and CT scan showed the presence of multiple gallstones and the situs viscerum inversus of the abdominal organs. The only pathological finding was cholecystolithiasis. Laparoscopic cholecystectomy was judged advisable. Situs viscerum inversus is not a contraindication for laparoscopic cholecystectomy. This abnormal anatomical condition may create some initial difficulty for the surgeons, because of the inverted position of the organs. The peculiarity of our case is the unlikely site of the abdominal pain, located in the epigastrium and on the right side although the patient had situs viscerum inversus. Laparoscopic cholecystectomy can be performed on the left-sided gallbladder proceeding with the "american technique". In difficult cases, open cholecystectomy can be unavoidable

Comparison of hemodynamic and respiratory effects of propofol and sevoflurane during carbon dioxide pneumoperitoneum in a swine model

The aim of this study was to compare intraoperative hemodynamic and respiratory parameters using propofol and sevoflurane during laparoscopic surgery in a porcine model. After induction of general anaesthesia in 16 pigs with fentanyl (0.005 mg kg(-1)) followed by propofol (6 mg Kg(-1)), it was maintained with fentanyl (0.01 mg kg(-1)h(-1)) and sevoflurane in O2 in group 1 (G1, n = 8) and fentanyl and propofol (12 mg kg(-1)h(-1)) in group 2 (G2, n = 8). The parameters monitored were heart rate, airway pressure (PAW), arterial and venous blood pressures and arterial blood gas analysis. The carbon dioxide pneumoperitoneum was maintained at 12 mmHg for 2 hours. Data were expressed as mean +/- standard deviation and were analysed using the Wilcoxon test (p < 0.05). G1 showed significantly higher PAW values than G2 at T60, T90 and T120. The heart rate values were significantly higher in G1 at T90 and T120. Middle arterial pressure was significantly lower in G1 than G2 at T30 and T60. The base deficit was significantly greater in G1 at T60, T90, T120 and Tpost. In this study propofol assured better hemodynamic and respiratory conditions than sevoflurane during laparoscopy in a porcine model

The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.

Chordin-mediated regulation of bone morphogenetic protein (BMP) family growth factors is essential in early embryogenesis and adult homoeostasis. Chordin binds to BMPs through cysteine-rich von Willebrand factor type C (vWC) homology domains and blocks them from interacting with their cell surface receptors. These domains also self-associate and enable chordin to target related proteins to fine-tune BMP regulation. The chordin-BMP inhibitory complex is strengthened by the secreted glycoprotein twisted gastrulation (Tsg); however, inhibition is relieved by cleavage of chordin at two specific sites by tolloid family metalloproteases. As Tsg enhances this cleavage process, it serves a dual role as both promoter and inhibitor of BMP signalling. Recent developments in chordin research suggest that rather than simply being by-products, the cleavage fragments of chordin continue to play a role in BMP regulation. In particular, chordin cleavage at the C-terminus potentiates its anti-BMP activity in a type-specific manner