Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

PURPOSE: Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. METHODS: Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. RESULTS: Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). CONCLUSION: Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Obstetric and neonatal outcomes following taxane use during pregnancy: a systematic review.

BACKGROUND: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited. METHODS: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken. RESULTS: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia. CONCLUSIONS: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety.

Cerebrovascular Complications Associated With Iatrogenic Fungal Meningitis Following Surgical Procedures in Mexico.

BACKGROUND: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with Fusarium solani among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis. METHODS: A retrospective case series of patients diagnosed with fungal meningitis following surgical procedures under contaminated epidural anesthesia who developed a unique pattern of CVC during their hospitalization. RESULTS: Three female patients (mean age, 35 years) with CVC due to iatrogenic fungal meningitis were included. Positive Fungitell ß-D-glucan assay in cerebrospinal fluid was documented in all cases, and F. solani was confirmed by polymerase chain reaction in case 3. All cases were complicated by severe vertebrobasilar circulation vasculopathy and arterial dissections with resultant subarachnoid hemorrhage and intraventricular hemorrhage, ultimately leading to patients' death. CONCLUSIONS: The death toll from the ongoing fungal meningitis outbreak keeps rising, underscoring the need for early recognition and aggressive treatment. We highlight the risk for vertebrobasilar circulation CVC among these patients. The angioinvasive nature of F. solani is yet to be clarified; however, a clear pattern has been observed. Public health awareness should be raised and a strong response should be pursued.

Risk Factors for Stroke After Carotid Paraganglioma Surgery.

BACKGROUND: The Carotid Paraganglioma Cooperative International Registry (CAPACITY) is an international registry composed of 1,432 patients with carotid body tumors (CBT) from 11 centers from 4 countries. The aim of this study was to identify risk factors for patients who presented stroke after carotid paraganglioma resection. METHODS: Clinical characteristics and demographics of patients who presented transoperatively and postoperatively stroke from the CAPACITY database were retrospectively gathered. Regression analysis was performed using single logistic regression with Omnibus' test for possible factors that might contribute to present stroke. RESULTS: Out of 1,432 patients, 8 (0.5%) female patients presented stroke. Median age was 53 years (range: 41-70 years). Six strokes occurred transoperatively, diagnosed clinically in the immediate postoperative period. Of them, none of the patients received any further treatment. Three of them died on postoperative day 2, 3, and 4. Two patients developed stroke during the first 24 postoperative hours, patients showed dysarthria, and aphasia. One of them was reintervened with thrombectomy due to thrombosis of the common carotid artery the other patient was treated conservatively. Median follow-up was 16 months (range: 2-72 months). Single logistic regression analysis revealed a history of diabetes mellitus (odds ratio (OR) 7.62), carotid artery disease (OR 17.51), and vascular lesion (OR 2.37) to have significantly increased odds of stroke during CBT surgery. CONCLUSIONS: In the present study history of diabetes mellitus, carotid artery disease, and vascular lesion had increased odds of stroke during CBT surgery. Findings are limited by low event rate and even larger cohorts are needed to fully define preventive preoperative strategies for preventing stroke.

Clinical Characteristics and Surgical Outcomes of Carotid Body Tumors: Data from the Carotid Paraganglioma Cooperative International Registry (CAPACITY) Group.

BACKGROUND: This study's objective was to conduct a multinational registry of patients with carotid body tumors (CBTs) and to analyze patients' clinical characteristics, treatments, and outcomes. METHODS: Retrospective study from the Carotid Paraganglioma Cooperative International Registry involving eleven medical centers in Bolivia, Ecuador, Mexico, and Spain, of all patients with a CBT who underwent resection between 2009 and 2019. RESULTS: A total of 1432 patients with a CBT surgically treated were included. Median patient age was 54 years (range: 45-63 years), and 82.9% (1184) of the study cohort were female. While at low altitude, the proportion of female-to-male cases was 2:1, at high altitude, this proportion increased to 8:1, with statistically significant differences (p = .022). Median operative time was 139 min (range: 110-180 min), while median operative blood loss was 250 ml (range: 100-500 ml), with statistically significant difference in increased blood loss (p = .001) and operative time (p = .001) with a higher Shamblin classification. Eight (0.6%) patients suffered stroke. Univariate analysis analyzing for possible factors associated with increased odds of stroke revealed intraoperative vascular lesion to present an OR of 2.37 [CI 95%; 1.19-4.75] (p = 0.001). In 245 (17.1%), a cranial nerve injury was reported. Seven (0.5%) deaths were recorded. CONCLUSION: The most common CBT type on this cohort was hyperplasic, which might be partially explained by the high altitudes where these patients lived. Increased blood loss and operative time were associated with a higher Shamblin classification, and the risk of stroke was associated with patients presenting transoperative vascular lesions.

A Call for Action for an Association of Program Directors in Surgery in Mexico.

General surgery (GS) residency remains among medical students' most pursued post-graduate training programs. However, the vast heterogeneity of GS programs in Mexico remains a cause of concern. For instance, as of 2018, among 169 official programs registered in Mexico, certified by 33 universities, all varied in size, location, academic activities, and surgeries performed. Establishing continuous, uniform, and modern education is of utmost importance. The development of a society solely dedicated to the training and formation of GS residents in Mexico may prove to be a valuable and efficient tool to tackle these issues. On this perspective, we call for action for the creation of a Program Directors Association in Surgery in Mexico to establish an action plan and implement changes that ensure high standards of surgical residencies around the nation. These ideas are relevant for all countries and should be promoted to develop strategies that enhance the quality of surgical education all-around.

Venous Thromboembolism in Hospitalized COVID-19 Patients Treated in a Single Academic Center in Mexico: A Case Series Study.

BACKGROUND: The increasing prevalence of venous thromboembolism (VTE) among patients with coronavirus disease 2019 (COVID-19) is a matter of concern as it contributes significantly to patients' morbidity and mortality. Data regarding the optimal anticoagulation regimen for VTE prevention and treatment remain scarce. This study describes the characteristics, treatment, and outcomes of COVID-19 patients with VTE treated in a single academic center in Mexico. METHODS: We conducted a retrospective study of all patients with a positive PCR test for SARS-CoV-2 hospitalized in a single academic center in Monterrey, Mexico, between March 2020 and February 2021, with a radiologically confirmed VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE). Informed consent was obtained from each patient before reviewing their medical records. RESULTS: Of the 2000 COVID-19 hospitalized patients, 36 (1.8%) developed VTE and were included in the analysis. The median age was 60 years (range 32-88 years), and up to 78% (n = 28) were males. Most patients (n = 34, 94%) had an underlying comorbidity and 47% (n = 17) had a BMI ≥ 30 kg/m2. In most cases (n=28, 78%), VTE presented as a PE, whereas the remaining 22% (n = 8) had a DVT. The median time between hospital admission and VTE was 8 days (range 0-33 days). Regarding the thromboprophylaxis regimen, 35/36 patients received low molecular weight heparin enoxaparin on admission, most commonly at a dose of 60 mg daily (n = 19, 53%). Other complications presented were superinfection (n = 19, 53%), acute kidney injury (n = 11, 31%), and septic shock (n = 5, 14%). A total of 69% of patients (n = 25) required intensive care unit admission, and patients' overall mortality was 55.6%. CONCLUSION: VTE remains a significant cause of increased morbidity and mortality among patients with COVID-19. The strikingly high mortality among patients with VTE highlights the need for further investigation regarding the best preventive, diagnostic, and treatment approaches.

Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with cancer are considered a priority group for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination given their high risk of contracting severe Coronavirus Disease 2019 (COVID-19). However, limited data exist regarding the efficacy of immunisation in this population. In this study, we assess the immunologic response after COVID-19 vaccination of cancer versus non-cancer population. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from 01st March 2020 through 12th August 12 2021. Primary end-points were anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) seroconversion rates, T-cell response, and documented SARS-CoV-2 infection after COVID-19 immunisation. Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models. RESULTS: This systematic review and meta-analysis included 35 original studies. Overall, 51% (95% confidence interval [CI], 41-62) and 73% (95% CI, 64-81) of patients with cancer developed anti-S IgG above the threshold level after partial and complete immunisation, respectively. Patients with haematologic malignancies had a significantly lower seroconversion rate than those with solid tumours after complete immunisation (65% vs 94%; P < 0.0001). Compared with non-cancer controls, oncological patients were less likely to attain seroconversion after incomplete (risk ratio [RR] 0.45 [95% CI 0.35-0.58]) and complete (RR 0.69 [95% CI 0.56-0.84]) COVID-19 immunisation schemes. Patients with cancer had a higher likelihood of having a documented SARS-CoV-2 infection after partial (RR 3.21; 95% CI 0.35-29.04) and complete (RR 2.04; 95% CI 0.38-11.10) immunisation. CONCLUSIONS: Patients with cancer have an impaired immune response to COVID-19 vaccination compared with controls. Strategies that endorse the completion of vaccination schemes are warranted. Future studies should aim to evaluate different approaches that enhance oncological patients' immune response.