7 research outputs found
Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy
IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical
attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced
colorectal cancers at diagnosis.
OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced
oncologic stage and change in clinical presentation for patients with colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all
17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December
31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period),
in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was
30 days from surgery.
EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery,
palliative procedures, and atypical or segmental resections.
MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer
at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as
cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding,
lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery,
and palliative surgery. The independent association between the pandemic period and the outcomes
was assessed using multivariate random-effects logistic regression, with hospital as the cluster
variable.
RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years)
underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142
(56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was
significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR],
1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic
lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03).
CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the
SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients
undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for
these patients
Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial
Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt
A new beta-chain haemoglobin variant with increased oxygen affinity: Hb Roma [beta115(g17)Ala-->Val]
Background
Haemoglobin Roma [β115(G17)Ala → Val] is a new adult haemoglobin variant found in a patient presenting a mild hypochromia and microcytosis. We studied this previously uncharacterised variant in order to evaluate the effect on the structural and funcional properties of the Ala → Val substitution at the α1β1 interface.
Methods and results
The variant chain was identified by direct DNA sequencing of the β-globin gene, which revealed a GCC → GTC mutation in codon 115. This mutation was confirmed by mass spectrometric analysis of the tetramers and peptides. The oxygen-binding properties of the haemoglobin A/haemoglobin Roma mixture, in which the variant makes up 25% of the haemoglobins, showed a significant increase in oxygen affinity with respect to normal haemoglobin A, both in the absence and presence of 2,3-bisphosphoglycerate. The role of the βG17 position, situated at the α1β1 interface, has been examined using computational models of haemoglobin Roma and other known βG17 variants, in comparison with normal haemoglobin A.
Conclusions
This study suggests that the β115(G17)Ala → Val substitution at the α1β1 interface is responsible for increased oxygen affinity and mild destabilisation of the haemoglobin Roma.
General significance
An amino acid substitution at the G17 position of the α1β1 interface may result in stabilisation of the high affinity R-state of the haemoglobin molecule
Change in Predicted 10-Year Cardiovascular Risk Following Roux-en-Y Gastric Bypass Surgery: Who Benefits?
The risk of developing cardiovascular disease is higher in obese than in non-obese individuals. Surgery for obesity is effective in reducing weight and resolution of diabetes, hypertension, and dyslipidemia. Our aim was to assess the estimated 10-year cardiovascular risk of obese patients before and after treatment of obesity with a gastric bypass. Weight, body mass index systolic and diastolic blood pressure, lipid profile, glycemia, and history of cardiovascular disease were obtained for obese patients before and 2 years after Roux-en-Y gastric bypass surgery. Ten-year cardiovascular risk was calculated using the Framingham score. Forty-two patients were included in the study. We observed a significant reduction (p < 0.05) of 10-year cardiovascular risk mainly associated with weight reduction and improvement of comorbidities associated with obesity. The benefits were greater among patients who already presented known risk factors such as diabetes and hypertension. Superobese patients benefited as early as 2 years after surgery, when weight loss was greater. Weight loss secondary to surgery was sustained after 2 years and promoted improvement of comorbidities, with an important reduction of 10-year cardiovascular risk especially among patients with previous risk factors
Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial
Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt
Defects of full-length dystrophin trigger retinal neuron damage and synapse alterations by disrupting functional autophagy
Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study
Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P = 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes