Instituto Jalisciense de Cancerología

BACKGROUND: In an early-phase study involving patients with advanced non-small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC. METHODS: In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. All the patients had received no previous chemotherapy. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more. RESULTS: Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P = 0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 months (95% CI, 12.2 to 15.1) with chemotherapy. The percentage of patients with grade 3 or 4 treatment-related adverse events in the overall population was 32.8% with nivolumab plus ipilimumab and 36.0% with chemotherapy. CONCLUSIONS: First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 227 ClinicalTrials.gov number, NCT02477826.).

BACKGROUND: Chemotherapeutic study of cervical squamous cell carcinoma has shown some positive results. Complete plus partial (overall) response rates of 15%-35% (complete response rate, less than 5%) were achieved with the use of a small number of cytotoxic single agents in patients with advanced disease. In addition, overall response rates of 60%-70% (complete response rates, 10%-20%) were achieved with cisplatin-based, multiagent regimens in patients with primary, locally advanced disease. However, the lack of clear evidence that existing chemotherapy can achieve a survival benefit, coupled with the worldwide annual deaths of hundreds of thousands of women from cervical cancer, indicates the urgent need for effective systemic therapy for this disease. PURPOSE: In view of the preclinical and clinical evidence that supports testing of the novel combination of 13-cis-retinoic acid (13-cRA) plus interferon-alpha (IFN-alpha) in cervical squamous cell carcinoma, we conducted a phase II study of this regimen in locally advanced disease. METHODS: Twenty-six patients with untreated, locally advanced squamous cell carcinoma of the cervix were treated daily for at least 2 months with oral 13-cRA (1 mg/kg) and subcutaneous recombinant human IFN alpha-2a (6 million units). In 21 patients (81%), the disease was stage II or higher. RESULTS: Thirteen patients (50%) experienced major responses (tumor regression greater than or equal to 50%) in association with resolution of symptoms; one achieved complete response, and 12 experienced partial response. Seven with partial response are improving further, four are being maintained in partial response, and one responder has relapsed during therapy. The response rate is 58% (11 of 19) in patients with stage IIB or higher disease and 66% (10 of 15) in patients with bulky disease (at least one dimension greater than or equal to 10 cm). Of the 13 non-responders, nine have stable disease and four have had disease progression during therapy. Toxicity was minimal. CONCLUSION: These preliminary results indicate that systemic 13-cRA plus IFN alpha-2a is a highly active, well-tolerated therapy for locally advanced cervical cancer.

AIMS: Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM. METHODS: Patients (N = 469) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA1c at 26 weeks. Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0%, change in fasting plasma glucose (FPG) and systolic blood pressure, and per cent change in body weight, high-density lipoprotein cholesterol, and triglycerides (weeks 26 and 52). RESULTS: HbA1c was significantly reduced with canagliflozin 100 and 300 mg vs. placebo at week 26 (-0.85%, -1.06%, and -0.13%; p < 0.001); these reductions were maintained at week 52 (-0.74%, -0.96%, and 0.01%). Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 (p < 0.001) and week 52. Overall adverse event (AE) rates were similar across groups over 52 weeks, with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo; these led to few discontinuations. Increased incidence of documented, but not severe, hypoglycaemia episodes was seen with canagliflozin vs. placebo. CONCLUSIONS: Canagliflozin improved glycaemic control, reduced body weight, and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks.

Over the last 500 years, admixture among Amerindians, Europeans, and Africans, principally, has come to shape the present-day gene pool of Mexicans, particularly Mestizos, who represent about 93% of the total Mexican population. In this work, we analyze the genetic data of 13 combined DNA index system-short tandem repeats (CODIS-STRs) in 1,984 unrelated Mestizos representing 10 population samples from different regions of Mexico, namely North, West, Central, and Southeast. The analysis of molecular variance (AMOVA) test demonstrated low but significant differentiation among Mestizos from different regions (F(ST) = 0.34%; P = 0.0000). Although the spatial analysis of molecular variance (SAMOVA) predicted clustering Mestizo populations into four well-delimited groups, the main differentiation was observed between Northwest when compared with Central and Southeast regions. In addition, we included analysis of individuals of Amerindian (Purepechas), European (Huelva, Spain), and African (Fang) origin. Thus, STRUCTURE analysis was performed identifying three well-differentiated ancestral populations (k = 3). STRUCTURE results and admixture estimations by means of LEADMIX software in Mestizo populations demonstrated genetic heterogeneity or asymmetric admixture throughout Mexico, displaying an increasing North-to-South gradient of Amerindian ancestry, and vice versa regarding the European component. Interestingly, this distribution of Amerindian ancestry roughly reflects pre-Hispanic Native-population density, particularly toward the Mesoamerican area. The forensic, epidemiological, and evolutionary implications of these findings are discussed herein.

BACKGROUND: Intramuscular gluteal lipoinjection has become one of the most commonly used surgical procedures for achieving improvement in the gluteal contour; however, there are few studies that report and analyze the causes of secondary death from this surgical procedure. METHODS: An analysis of secondary deaths from gluteal lipoinjection procedures was performed in Mexico and Colombia over periods of 10 and 15 years, respectively. In Mexico, the study was performed through a survey of all members of the Mexican Association of Reconstructive, Plastic and Aesthetic Surgery. In Colombia, the study was performed through an analysis of deaths and autopsies documented by the National Institute of Legal Medicine and Forensic Sciences Regional Bogotá. RESULTS: A total of 413 Mexican plastic surgeons reported 64 deaths related to liposuction, with 13 deaths caused by gluteal lipoinjection. In Colombia, nine deaths were documented. Of the 13 deaths in Mexico, eight (61.6 percent) occurred during lipoinjection, whereas the remaining five (38.4 percent) occurred within the first 24 hours. In Colombia, six deaths (77.7 percent) occurred during surgery and three occurred (22.2 percent) immediately after surgery. In the Colombian autopsy results, seven cases of macroscopic fat embolism and two cases with a microscopic embolism were reported, with abundant fatty tissue in the infiltrated gluteal muscles. CONCLUSIONS: In this study, the authors found that intramuscular gluteal lipoinjection is associated with mortality caused by gluteal blood vessel damage allowing macroscopic and microscopic fat embolism; therefore, buttocks lipoinjection should be performed very carefully, avoiding injections into deep muscle planes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery. METHODS: The American Society of Peritoneal Surface Malignancies (ASPSM) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C (MMC), stratifying them by the Peritoneal Surface Disease Severity Score (PSDSS). RESULTS: Median overall survival (OS) of 539 patients with complete cytoreduction was 32.6 months, 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group (P = 0.925). However, when stratified by PSDSS, median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin (P = 0.012), whereas in PSDSS III/IV patients, median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin (P = 0.427). CONCLUSION: These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC, favorable histologies and low burden of disease (PSDSS I/II) undergoing complete cytoreduction. Prospective studies are warranted, which stratify patients by their PSDSS and randomize them to HIPEC with MMC vs. Oxaliplatin.

BACKGROUND: Acne vulgaris is an exceedingly common condition in adolescence and may extend into adult life in some individuals. Even though this condition is at times minimized, it has been found to have a profound impact in the quality of life of many affected individuals. Acne scarring can be even more of a source of psychological and social problems than active acne is, and when inadequately treated, the latter can lead to the former. Moderate and severe acne vulgaris usually require a regimen of systemic and/or topical medications, which are given for several months or even years and frequently require multiple visits to the physician office, the laboratory, etc. This results in loss of time at school and considerable expense. Side effects from medications and the frequent need to use alternative drugs when there is no response to medical treatment are possible. OBJECTIVE: To evaluate the role of a novel medical device that uses radiofrequency as a source of energy to produce volumetric tissue heating, while sparing the epidermis, allowing for a procedure with no down time and no postoperative care required. METHODS: Twenty-two patients, 10 women and 12 men, ranging in age from 16 to 28, with moderate to severe, scarring, cystic, active, acne vulgaris participated. Only nine of these patients were on concomitant medical treatment such as oral antibiotics or topical agents. All 22 patients were treated with a new nonablative radiofrequency unit, which delivers a concomitant spray of cryogen for epidermal sparing. One session was done in 20 patients and two sessions in 2 patients. The average fluence per energy delivery was 72 J/cm2. Follow-up ranged from 1 to 8 months. Patient questionnaires and active acne lesion counts were used to evaluate the response to treatment. RESULTS: Excellent response was seen in 82% (n=18). Modest response was seen in 9% (n=2), and no response was seen in 9% (n=2); t-test on active lesion counts before treatment and after treatment was less than 0.009004. No side effects were identified on any of these patients. No down time from the procedure was seen. Only topical anesthesia, ELA-Max 5% (Ferndale Labs, Ferndale, MI) was used; 59% of patients were on no acne medication before, during, or after the procedure. CONCLUSIONS: Nonablative radiofrequency appears to be a new safe and effective treatment alternative for moderate to severe acne vulgaris. Further research is in progress to evaluate this treatment modality in a larger number of patients.

PURPOSE Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR -mutant, metastatic non–small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837 ). METHODS Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS. RESULTS Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients. CONCLUSION Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans. Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.

LBA9000 Background: EGFR TKIs are standard 1L therapy for metastatic NSCLC with sensitizing EGFR mutations; however, most patients (pts) ultimately experience PD. We report the protocol-specified final analysis (FA) from the randomized, double-blind, phase 3 KEYNOTE-789 study of pemetrexed (pem) and platinum-based chemotherapy (chemo) with or without pembrolizumab (pembro) as subsequent therapy for pts with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC (NCT03515837). Methods: Adults with histologically or cytologically confirmed stage IV nonsquamous NSCLC, ECOG PS of 0 or 1, documented DEL19 or L858R EGFR mutation, and progression after EGFR TKI treatment were enrolled. Pts were randomized 1:1 to 35 cycles of pembro 200 mg Q3W or placebo (pbo) Q3W plus 4 cycles of pem and carboplatin or cisplatin Q3W followed by maintenance pem. Randomization was stratified by PD-L1 TPS (&lt;50% vs ≥50%), prior osimertinib (yes vs no), and region (East Asia vs not East Asia). Dual primary endpoints were PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. ORR and DOR per RECIST v1.1 by BICR and safety were secondary endpoints. Final PFS testing was completed at the second interim analysis (IA2; data cutoff, Dec 3, 2021); all other endpoints were assessed at FA (data cutoff, Jan 17, 2023). Efficacy boundaries based on actual observed events were 1-sided P = 0.0117 for PFS (IA2) and P = 0.0118 for OS (FA). Results: 492 pts were randomized to pembro + chemo (n = 245) or pbo + chemo (n = 247). At IA2, median PFS (95% CI) was 5.6 (5.5–5.8) mo with pembro + chemo vs 5.5 (5.4–5.6) mo with pbo + chemo; HR 0.80 (95% CI, 0.65–0.97); P = 0.0122; and the results did not reach statistical significance. Median (range) time from randomization to data cutoff at FA (Jan 17, 2023) was 42.0 (29.5–53.9) mo. At FA, median OS (95% CI) was 15.9 (13.7–18.8) vs 14.7 (12.7–17.1) mo. While the HR for OS (0.84 [95% CI, 0.69–1.02]; P = 0.0362) favored pembro + chemo vs pbo + chemo, it did not reach statistical significance. OS rates at 12-mo were 61.6% vs 59.4% and at 24-mo were 30.6% vs 26.4%. HR for OS was similar in PD-L1 TPS ≥50% (HR, 0.84) and TPS &lt;50% groups (HR, 0.85). ORR (95% CI) in ITT was 29.0% (23.4%–35.1%) with pembro + chemo vs 27.1% (21.7%–33.1%) with pbo + chemo. Median DOR was 6.3 (2.3 to 40.8+) mo vs 5.6 (1.8+ to 40.6+) mo. Grade ≥3 treatment-related AEs occurred in 43.7% of pts in pembro + chemo arm and 38.6% in pbo + chemo arm; grade 5 AEs occurred in 0.4% vs 0.8%. Grade ≥3 immune-mediated AEs and infusion reactions occurred in 4.5% of pts in the pembro + chemo arm and 2.0% in the pbo + chemo arm; 0.4% vs 0% had grade 5 events. Conclusions: In the KEYNOTE-789 study, addition of pembro to chemo in pts with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS and OS in comparison to pbo + chemo. AEs were manageable in both arms, and no new safety signals were identified. Clinical trial information: NCT03820986 .

OBJECTIVE: In patients with systemic lupus erythematosus (SLE), evidence suggests that most vaccines (except live-virus vaccines) are safe, although antibody response may be reduced. This substudy from the phase III, randomized, double-blind, placebo-controlled BLISS-76 trial evaluated the effects of belimumab on preexisting antibody levels against pneumococcal, tetanus, and influenza antigens in patients with SLE. METHODS: In BLISS-76, patients with autoantibody-positive, active SLE were treated with placebo or belimumab 1 or 10 mg/kg every 2 weeks for 28 days and every 28 days thereafter, plus standard SLE therapy, for 76 weeks. This analysis included a subset of patients who had received pneumococcal or tetanus vaccine within 5 years or influenza vaccine within 1 year of study participation. Antibodies to vaccine antigens were tested at baseline and Week 52, and percentage changes in antibody levels from baseline and proportions of patients maintaining levels at Week 52 were assessed. Antibody titers were also assessed in a small number of patients vaccinated during the study. RESULTS: Consistent with preservation of the memory B cell compartment with belimumab treatment, the proportions of patients maintaining antibody responses to pneumococcal, tetanus, and influenza antigens were not reduced. In a small group receiving influenza vaccine on study, antibody responses were frequently lower with belimumab, although titer levels were > 1:10 in all patients treated with 10 mg/kg and in the majority treated with 1 mg/kg. CONCLUSION: Treatment with belimumab did not affect the ability of patients with SLE to maintain antibody titers to previous pneumococcal, tetanus, and influenza immunizations. [ClinicalTrials.gov registration number NCT 00410384].

Cirrhosis represents the third cause of mortality among Mexican people of productive age.1 Several drugs have been tested in the clinical scenario2,3 although conclusive evidence concerning drug efficacy has proven elusive. PFD is an orally bioavailable pyridone derivative (5-methyl-1-phenyl-2-(1H)-pyridone) that affects a variety of profibrogenic cytokines and its mechanism of action mostly resides in its anti-inflammatory and antifibrotic activity.4–6 Here we present data obtained from a pilot clinical trial evaluating the safety and efficacy of PFD in 15 patients with established advanced liver disease caused by hepatitis C virus chronic infection. This is the first report showing improvements in liver histology (that is, necrosis, inflammation, steatosis, fibrosis, and cell regeneration) 12 months after PFD therapy. Colour Doppler ultrasound guided liver biopsies were obtained at baseline and after 12 months of PFD treatment and evaluated for stage of fibrosis and grade of activity according to the modified …

PURPOSE: Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. METHODS: In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. RESULTS: Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. CONCLUSION: In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.

Approximately 25-50% of the population worldwide exhibits serum triglycerides (TG) (≥150 mg/dL) which are associated with an increased level of highly atherogenic remnant-like particles, non-alcoholic fatty liver disease, and pancreatitis risk. High serum TG levels could be related to cardiovascular disease, which is the most prevalent cause of mortality in Western countries. The etiology of hypertriglyceridemia (HTG) is multifactorial and can be classified as primary and secondary causes. Among the primary causes are genetic disorders. On the other hand, secondary causes of HTG comprise lifestyle factors, medical conditions, and drugs. Among lifestyle changes, adequate diets and nutrition are the initial steps to treat and prevent serum lipid alterations. Dietary intervention for HTG is recommended in order to modify the amount of macronutrients. Macronutrient distribution changes such as fat or protein, low-carbohydrate diets, and caloric restriction seem to be effective strategies in reducing TG levels. Particularly, the Mediterranean diet is the dietary pattern with the most consistent evidence for efficacy in HTG while the use of omega-3 supplements consumption is the dietary component with the highest number of randomized clinical trials (RCT) carried out with effective results on reducing TG. The aim of this review was to provide a better comprehension between human nutrition and lipid metabolism.

BACKGROUND: Dexamethasone has been reported to reduce postoperative symptoms after different surgical procedures. We evaluated the efficacy of preoperative dexamethasone in ameliorating postoperative nausea and vomiting (PONV), and pain after mastectomy. METHODS: In this prospective, double-blind, placebo-controlled study, 70 patients scheduled for mastectomy with axillary lymph node dissection were analyzed after randomization to treatment with 8 mg intravenous dexamethasone (n = 35) or placebo (n = 35). All patients underwent standardized procedures for general anesthesia and surgery. Episodes of PONV and pain score were recorded on a visual analogue scale. Analgesic and antiemetic requirements were also recorded. RESULTS: Demographic and medical variables were similar between groups. The incidence of PONV was lower in the dexamethasone group at the early postoperative evaluation (28.6% vs. 60%; p = 0.02) and at 6 h (17.2% vs. 45.8%; p = 0.03). More patients in the placebo group required additional antiemetic medication (21 vs. 8; p = 0.01). Dexamethasone treatment significantly reduced postoperative pain just after surgery (VAS score, 4.54 ± 1.55 vs. 5.83 ± 2.00; p = 0.004), at 6 h (3.03 ± 1.20 vs. 4.17 ± 1.24; p < 0.0005) and at 12 h (2.09 ± 0.85 vs. 2.54 ± 0.98; p = 0.04). Analgesics were required in more patients of the control group (21 vs. 10; p = 0.008). There were no adverse events, morbidity or mortality. CONCLUSIONS: Preoperative intravenous dexamethasone (8 mg) can significantly reduce the incidence of PONV and pain in patients undergoing mastectomy with axillary dissection for breast cancer. TRIAL REGISTRATION NUMBER: NCT01116713.

The objective of the present study was to identify volatile prints from exhaled breath, termed breath-print, from breast cancer (BC) patients and healthy women by means of an electronic nose and to evaluate its potential use as a screening method. A cross-sectional study was performed on 443 exhaled breath samples from women, of whom 262 had been diagnosed with BC by biopsy and 181 were healthy women (control group). Breath-print analysis was performed utilizing the Cyranose 320 electronic nose. Group data were evaluated by principal component analysis (PCA), canonical discriminant analysis (CDA), and support vector machine (SVM), and the test's diagnostic power was evaluated by means of receiver operating characteristic (ROC) curves. The results obtained using the model generated from the CDA, which best describes the behavior of the assessed groups, indicated that the breath-print of BC patients was different from that of healthy women and that they presented with a variability of up to 98.8% and a correct classification of 98%. The sensitivity, specificity, negative predictive value, and positive predictive value reached 100% according to the ROC curve. The present study demonstrates the capability of the electronic nose to separate between healthy subjects and BC patients. This research could have a beneficial impact on clinical practice as we consider that this test could probably be used at the first point before the application of established gold tests (mammography, ultrasound, and biopsy) and substantially improve screening tests in the general population.

Infrared thermography is a technique that can detect anomalies in temperature patterns which can indicate some breast pathologies including breast cancer. One limitation of the method is the absence of standardised thermography interpretation procedures. Deep learning models have been used for pattern recognition and classification of objects and have been adopted as an adjunct methodology in medical imaging diagnosis. In this paper, the use of a deep convolutional neural network (CNN) with transfer learning is proposed to automatically classify thermograms into two classes (normal and abnormal). A population of 311 female subjects was considered analysing two approaches to test the CNN’s performance: one with a balanced class distribution and the second study in a typical screening cohort, with a low prevalence of abnormal thermograms. Results showed that the transfer-learned ResNet-101 model had a sensitivity of 92.3% and a specificity of 53.8%, while with an unbalanced distribution the values were 84.6% and 65.3%, respectively. These results suggest that the model presented in this work can classify abnormal thermograms with high sensitivity which validates the use of infrared thermography as an adjunct method for breast cancer screening.

Background CheckMate 9KD ( NCT03338790 ) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib. Methods CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0–1. Cohort A1 included patients with postchemotherapy mCRPC (1–2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 mg every 4 weeks plus rucaparib 600 mg two times per day (nivolumab dosing ≤2 years). Coprimary endpoints were objective response rate (ORR) per Prostate Cancer Clinical Trials Working Group 3 and prostate-specific antigen response rate (PSA 50 -RR; ≥50% PSA reduction) in all-treated patients and patients with homologous recombination deficiency (HRD)-positive tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results Outcomes (95% CI) among all-treated, HRD-positive, and BRCA1/2 -positive populations for cohort A1 were confirmed ORR: 10.3% (3.9–21.2) (n=58), 17.2% (5.8–35.8) (n=29), and 33.3% (7.5–70.1) (n=9); confirmed PSA 50 -RR: 11.9% (5.9–20.8) (n=84), 18.2% (8.2–32.7) (n=44), and 41.7% (15.2–72.3) (n=12); median rPFS: 4.9 (3.7–5.7) (n=88), 5.8 (3.7–8.4) (n=45), and 5.6 (2.8–15.7) (n=12) months; and median OS: 13.9 (10.4–15.8) (n=88), 15.4 (11.4–18.2) (n=45), and 15.2 (3.0–not estimable) (n=12) months. For cohort A2 they were confirmed ORR: 15.4% (5.9–30.5) (n=39), 25.0% (8.7–49.1) (n=20), and 33.3% (7.5–70.1) (n=9); confirmed PSA 50 -RR: 27.3% (17.0–39.6) (n=66), 41.9 (24.5–60.9) (n=31), and 84.6% (54.6–98.1) (n=13); median rPFS: 8.1 (5.6–10.9) (n=71), 10.9 (6.7–12.0) (n=34), and 10.9 (5.6–12.0) (n=15) months; and median OS: 20.2 (14.1–22.8) (n=71), 22.7 (14.1–not estimable) (n=34), and 20.2 (11.1–not estimable) (n=15) months. In cohorts A1 and A2, respectively, the most common any-grade and grade 3–4 treatment-related adverse events (TRAEs) were nausea (40.9% and 40.8%) and anemia (20.5% and 14.1%). Discontinuation rates due to TRAEs were 27.3% and 23.9%, respectively. Conclusions Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naïve mCRPC, particularly those harboring BRCA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial. Trial registration number NCT03338790 .

Latin America (including Mexico and Central and South America) hosts a substantial proportion of global biodiversity, but suffers from increasing rates of deforestation, land degradation, and dryland expansion. Low-cost modification of local management practices integrating ecological restoration could play a major role in abating ecosystem degradation and biodiversity loss. A regional ecological restoration network would identify the major challenges, both practical and intellectual, and generate protocols for assisting land managers and stakeholders through shared databases and experience. Such a network would enhance the critical mass of practitioners working under similar, though diverse social, cultural, and ecological contexts. Una proporción sustancial de la biodiversidad mundial se encuentra en América Latina (la cual incluye a México, Centro y Sudamérica); sin embargo, esta región sufre de tasas crecientes de deforestación, degradación del suelo y expansión de las zonas áridas. Algunas prácticas locales de manejo, con modificaciones de bajo costo que integren la restauración ecológica, podrían jugar un papel muy importante en el abatimiento de la degradación de los ecosistemas y en la reducción de la biodiversidad. Una red de restauración ecológica regional identificaría los principales retos, tanto prácticos como intelectuales, y generaría los protocolos para auxiliar a los administradores y los dueños de terreno a través de experiencias y bases de datos compartidas. Esta red incrementaría la masa crítica de investigadores que trabajan en contextos sociales, históricos y ecológicos similares.

Mestizos currently represent most of the Mexican population (>90%); they are defined as individuals born in the country having a Spanish-derived last name, with family antecedents of Mexican ancestors back at least to the third generation. Mestizos are result of 500 years of admixture mainly among Spaniards, Amerindians, and African slaves. Consequently, a complex genetic pattern has been generated throughout the country that has been scarcely studied from the paternal point of view. This fact is important, taking into account that gene flow toward the New World comprised largely males. We analyzed the population structure and paternal admixture of present-day Mexican-Mestizo populations based on Y-STRs. We genotyped at least 12 Y-STRs in DNA samples of 986 males from five states: Aguascalientes (n = 293); Jalisco (n = 185); Guanajuato (n = 168); Chiapas (n = 170); and Yucatán (n = 170). AmpFlSTR Y-filer and Powerplex-Y(R) kits were used. Inclusion of North and Central Y-STR databases in the analyses allowed obtaining a Y-STR variability landscape from Mexico. Results confirmed the population differentiation gradient previously noted in Mestizos with SNPs and autosomal STRs throughout the Mexican territory: European ancestry increments to the Northwest and, correspondingly, Amerindian ancestry increments to the Center and Southeast. In addition, SAMOVA test and Autocorrelation Index for DNA Analysis autocorrelogram plot suggested preferential gene flow of males with neighboring populations in agreement with the isolation-by-distance model. Results are important for disease-risk studies (principally male-related) and for human identification purposes, because Y-STR databases are not available on the majority of Mexican-Mestizo populations.