Hyperbaric oxygen therapy increases the effect of 5-fluorouracil chemotherapy on experimental colorectal cancer in mice.

Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice.

Fatores clínicos associados à sobrevida de pacientes com COVID-19 internados em Unidade de Terapia Intensiva / Clinical factors associated with survival of patients with COVID-19 admitted to the Intensive Care Unit / Factores clínicos asociados a supervivencia de pacientes con COVID-19 ingresados a Unidad de Cuidados Intensivos

Objetivo:identificar fatores clínicos associados à sobrevida de pacientes com COVID-19 internados em Unidade de Terapia Intensiva. Método:estudo de coorte retrospectivo, por meiode análise documental de 100 prontuários de pacientes com COVID-19 internados em uma Unidade de Terapia Intensiva, no período marçoa maio de 2021. Resultados:os fatores sociodemográficos, comorbidades e fatores de risco indicaram mudança no perfil do paciente, em comparação aestudos realizados na primeira onda pandêmica. Dentre os fatores associados à sobrevida dos pacientes com COVID-19 internados em Unidade de Terapia Intensiva destacam-se a oxigenoterapia de baixo fluxo via nasal, a posição autoprona, a sedação com midazolam e o tempo de internação. Já a hemodiálise e o uso de rocurônio aumentaram o risco de óbito dos pacientes. Conclusão:os resultados podem contribuir para a tomada de decisões e melhorar o atendimento ao paciente crítico com COVID-19.

Objective:to identify clinical factors associated with the survival of patients with COVID-19 admitted to the Intensive Care Unit. Method:retrospective cohort study, through documentary analysis of 100 medical records of patients with COVID-19 admitted to an Intensive Care Unit, in the period from Marchto May 2021. Results:sociodemographic factors, comorbidities,and risk factors indicated a change in the patient's profile, compared to studies carried out in the first pandemic wave. Among the factors associated with the survival of patients with COVID-19 admitted to the Intensive Care Unit, low-flow nasal oxygen therapy, prone position, sedation with midazolam and length of stay stand out. Hemodialysis and the use of rocuronium increased the risk of death for patients. Conclusion:the results can contribute to decision-making and improve care for critical patients with COVID-19

Objetivo:identificar factores clínicos asociados a la supervivencia de pacientes con COVID-19 ingresados en la Unidad de Cuidados Intensivos. Método:estudio de cohorte retrospectivo, mediante análisis documental de 100 historias clínicas de pacientes con COVID-19 ingresados en una Unidad de Cuidados Intensivos, en el período de marzoa mayo de 2021. Resultados:factores sociodemográficos, comorbilidades y factores de riesgo indicaron un cambio en el perfil del paciente, en comparación con estudios realizados en laprimera ola pandémica. Entre los factores asociados a la supervivencia de los pacientes con COVID-19 ingresados en la Unidad de Cuidados Intensivos destacan la oxigenoterapia nasal de bajo flujo, la posición prona, la sedación con midazolam y el tiempo deestancia hospitalaria. La hemodiálisis y el uso de rocuronio aumentaron el riesgo de muerte de los pacientes. Conclusión:los resultados pueden contribuir a la toma de decisiones y mejorar la atención al paciente crítico con COVID-19

Risk of Sarcopenia Identified by Sarc-Calf, Nutritional Status and Hand Grip Strength in Patients with Hematological Cancer.

Background: Hematological cancer patients are prone to the development of sarcopenia and impaired nutritional and functional status. SARC-CalF is a screening tool for the risk of sarcopenia that has shown good results in this population. This study aimed to identify the risk of sarcopenia by SARC-CalF and to verify its association with nutritional status and Hand Grip Strength (HGS) in patients with hematological cancer. Materials and Methods: Adult patients, of both sexes, with hematological cancer, and in outpatient care participated in the study. We measured the Hand Grip Strength of the Dominant Hand (HGSD) and the Adductor Pollicis Muscle Thickness of the Dominant Hand (APMTD). Moreover, we applied the Patient-Generated Subjective Global Assessment (PG-SGA) and SARC-CalF. Data were analyzed with SPSS® software, 22.0, with a significance level of 5.0%. Results: Fifty-one patients aged an average of 60.4 ± 15.1 years were evaluated. Of those, 58.8% were elderly, 51% female, and 80.4% declared themselves non-white. The predominant diagnosis was Mature B Lymphoid Cell Neoplasia (37.7%), and 60.8% of the patients had a diagnosis time of ≤ 3 years. PG-SGA revealed that 35.3% of the patients were malnourished; APMTD and HGSD revealed that 60.8% and 25.5% had reduced muscle strength, respectively. SARC-CalF exposed that 39.2% of the patients were at risk for sarcopenia. Significant associations were found between SARC-CalF and diagnosis time ≤ 3 years (p = 0.039), PG-SGA (p = 0.020), APMTD (p = 0.039) and HGSD (p = 0.002). After binary logistic regression adjusted for age and sex, the reduced HGSD remained associated with the risk of sarcopenia. Conclusion: SARC-CalF identified a risk of sarcopenia in 39.2% of patients. The reduced HGSD was associated with the risk of sarcopenia.

Choristoma: a very rare cause of thyroid nodule. Case report and literature review.

BACKGROUND: Choristoma is a well-defined benign lesion formed by histologically normal tissue in an unusual location. Diagnosis is confirmed after surgical removal of the mass. To our knowledge, to date there has been only one case of thyroid choristoma described in the literature. PATIENT FINDINGS: A 70-year-old man with a history of non-Hodgkin lymphoma presented with sudden cervical enlargement. Cervical CT scan showed a 47mm hypodense nodule on the right thyroid lobe. Fine-needle aspiration revealed follicular lesion of undetermined significance. During the following weeks there was noticeable thyroid enlargement. Reassessment with thyroid ultrasound showed a 73mm nodule. The patient underwent total thyroidectomy. Histopathological examination revealed a choristoma composed of squamous epithelium lined cysts, smooth muscle, adipose tissue, connective tissue, foci of ossification and extramedullary hematopoiesis. No cytological atypia or tumoral necrosis were found. Thyroid choristomas are an exceedingly rare cause of a thyroid nodule.

Factors associated with surgical resection in patients with Crohn's disease: long-term evaluation.

PURPOSE: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). METHODS: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. RESULTS: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). CONCLUSIONS: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.

Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn's disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.

eTEP Rives-Stoppa impact on abdominal contour: a retrospective observational and clinical quality improvement study using Ellipse 9 tool.

BACKGROUND: The eTEP Rives-Stoppa (RS) procedure, increasingly used for ventral hernia repair, has raised concerns about postoperative upper abdominal bulging. This study aims to objectively evaluate changes in the abdominal contour after eTEP RS and explore potential causes using a novel analytical tool, the Ellipse 9. METHODS: Thirty patients undergoing eTEP RS without posterior rectus sheath closure were assessed before and 3 months after surgery using CT scan images. Key measurements analyzed included the distance between linea semilunaris (X2), eccentricity over the Cord (c/a Cord), superior eccentricity (c/a Sup), Y2, and the superior perimeter of the abdomen. The Ellipse 9 tool, which provides graphical images and numerical representations, was utilized alongside patient-reported outcomes to assess perceived abdominal changes. RESULTS: The study group exhibited a trend toward a flatter abdomen with reduced distance between linea semilunaris(X2). However, 17% of patients developed upper abdominal bulging (5). Significant differences in c/a Cord, c/a Sup, Y2, and the superior perimeter of the abdomen, confirmed with Bonferroni corrections, were noted between bulging (5 patients) and non-bulging groups (25 patients). There was a notable disparity between patient perceptions and objective outcomes. CONCLUSION: The eTEP RS procedure improved abdominal contour in most patients from a selected cohort. The Ellipse 9 tool was valuable for the objective analysis of these changes. The cause of bulging post-eTEP RS is probably multifactorial. Notably, there was often a discrepancy between patient perceptions of bulging and objective clinical findings.

Waist Circumference as a Tool for Identifying Visceral Fat in Women with Non-Metastatic Breast Cancer.

Abdominal adiposity is associated with tumor development and poor clinical outcomes in breast cancer (BC) and can be identified by the measurement of waist circumference (WC) and visceral adipose tissue (VAT). This study aimed to evaluate the association between waist circumference (WC) and imaging measurement of central adiposity according to age group in women with BC. Abdominal adiposity was assessed by WC and VAT, obtained by dual-energy X-ray absorptiometry (DXA). Body mass index (BMI) was assessed. The presence of inflammation was investigated by measuring C-Reactive Protein (CRP) levels. Multivariate linear regression models were applied to verify the association between WC and VAT. The significance level adopted for all tests was 5%. This study included 112 women with a mean age of 55.5 ± 11.4 years. After adjusted models, WC remained associated with VAT and for every centimeter increase in WC, there was an increase of 3.12 cm2 (CI: 2.40 - 3.85; p < 0.001) in VAT. WC was associated with VAT in women with breast cancer, proving to be a simple, fast, and noninvasive approach that can be used as a proxy to identify visceral fat.

Skeletal muscle mass obtained by anthropometric equation and presence of sarcopenia in postmenopausal women

Abstract Objective: To analyze the amount of muscle and the presence of sarcopenia in postmenopausal women using different methods, verifying the agreement between them as to skeletal muscle mass (SMM). Methods: This cross-sectional observational study was conducted with postmenopausal women aged ≥ 50 years. SMM was obtained from a predictive equation, Bioelectrical Impedance (BIA), and Dual Energy X-Ray Absorptiometry (DXA). The skeletal muscle mass index (SMI) and the appendicular skeletal muscle mass index (ASMI) were calculated. The cut-off point of SMI was determined for the population itself. The agreement between the SMI obtained using the different methods was verified. Sarcopenia was diagnosed according to the criteria proposed by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). The significance level adopted for all tests was 5.0%. Results: A total of 112 women were evaluated, with an average age of 66.1 ± 5.65 years. Among them, 51.8% were sufficiently active and 43.8% were overweight and obese. The SMI cut-offs were 6.46 kg/m2 for the predictive equation and 7.66 kg/m2 for BIA, with high sensitivity and specificity. There was an excellent agreement in the identification of SMM by the predictive equation (0.89 [0.824-0.917], p < 0.001) and BIA (0.92 [0.883-0.945], p < 0.001), in reference to DXA. The prevalence of sarcopenia was 0.9%, 1.8%, and 2.7% according to BIA, DXA, and the predictive equation, respectively. Conclusion: The predictive equation showed the expected agreement in estimating skeletal muscle mass in postmenopausal women, offering a viable and accurate alternative.

Factors associated with surgical resection in patients with Crohn's disease: long-term evaluation

Purpose: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). Methods: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. Results: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). Conclusions: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.

Impact on Anesthetic Agent Consumption After Autonomic Neural Blockade as Part of a Combined Anesthesia Protocol: A Randomized Clinical Trial.

BACKGROUND: The intraoperative autonomic neural blockade (ANB) was found safe and effective in controlling pain and associated symptoms and reducing analgesic consumption after laparoscopic sleeve gastrectomy (LSG). This study evaluated whether ANB performed at the outset of LSG reduces anesthetic consumption and promotes hemodynamic stability. METHODS: This prospective, double-blinded, randomized trial involved patients undergoing LSG in 2 high-volume institutions. Patients were randomized to receive ANB either at the onset or the end of the procedure. The primary outcome measure was the consumption of remifentanil and sevoflurane. Secondary outcomes included Aldrete scale score differences in the recovery room and hemodynamic stability during the surgery. RESULTS: In total, 80 patients (40 in the ANB at the onset group and 40 in the control group) were included for analysis. The consumption of remifentanil was significantly lower in the onset group compared to the control group (mean difference -0.04 mcg/kg/min, 95% confidence interval [CI], -0.06 to -0.02; P < .0001). There were no differences in the Aldrete scale scores between the 2 groups. Mean heart rate (HR) and mean arterial pressure (MAP) were also significantly less during surgery in the ANB at the onset group. No complications related to the ANB occurred. CONCLUSIONS: Performing ANB at the onset of LSG is a safe and effective approach that reduces remifentanil consumption and promotes hemodynamic stability during the procedure. This technique holds promise for optimizing anesthesia management in LSG and other minimally invasive surgeries.

Ectopic Intrathyroidal Parathyroid Adenoma Presenting With Osteoporotic Fractures in a Young Man: A Case Report.

Primary hyperparathyroidism (PHPT) can be associated with osteoporosis (OP) and fractures. We present a case of a 49-year-old male referred to our osteoporosis outpatient clinic due to a right femur osteoporotic fracture. At the age of 38, a right plantar nodular lesion was excised, and its histology was compatible with a deep dermis nodule formed by mononuclear and giant osteoclast-like cells. He has reported osteoporotic fractures since age 39 and renal colic episodes since age 45. His father had lipomas and renal colic episodes, and his paternal grandmother had lipomas. The laboratory evaluation was compatible with PHPT. A cervical ultrasound showed a 10mm single solid nodule in the left thyroid lobe, strongly hypoechogenic, with microcalcifications. Its cytology showed parathyroid tissue without atypia. Parathyroid scintigraphy had no uptake. A dual-energy X-ray absorptiometry scan showed a femoral neck Z-score of -4.3. He started alendronate/cholecalciferol (70mg/5600IU) weekly. He was submitted to a left hemithyroidectomy. Its histology showed an intrathyroidal parathyroid adenoma. Ectopic parathyroid adenomas are rare, of which 0.7%-6% are intrathyroidal. The excised foot lesion could be a brown tumour. Furthermore, calcium metabolism evaluation at that time might have allowed a PHPT diagnosis and its morbidity prevention. Osteoporotic fractures in young men must alert to secondary OP.

Meaning of Life Therapy: A Pilot Study of a Novel Psycho-Existential Intervention for Palliative Care in Cancer.

Intervention in Palliative Care aims to provide physical, psychosocial, and spiritual relief for patients and family members. Brief interventions with a psycho-existential approach have shown positive responses; however, cultural adaptations are needed. This pilot study aimed to develop the Meaning of Life Therapy (MLT), a novel psycho-existential intervention, rooted in the Dignity Therapy, Life Review, and Meaning-Centered Psychotherapy. MLT was culturally adapted to the Portuguese context to include questions about forgiveness, apology, reconciliation, farewell, and a legacy document, i.e., the Life Letter. Nine PC cancer patients answered a 14-question MLT protocol, intended to help patients find purpose and meaning in life. Eight themes emerged: Family, Preservation of Identity, Life Retrospective, Clinical Situation, Achievements, Socio-Professional Valorization, Forgiveness/Apology/Reconciliation, and Saying Goodbye. MLT has proved its ability to respond to the psycho-existential needs of PC patients. Further studies should be conducted to gain extensive knowledge of the effectiveness of culturally responsive interventions.

Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes.

BACKGROUND: Sarcomas are a rare and diverse group of cancers occurring mainly in young individuals for which an underlying germline genetic cause remains unclear in most cases. METHODS: Germline DNA from 177 children, adolescents and young adults with soft tissue or bone sarcomas was tested using multigene panels with 113 or 126 cancer predisposing genes (CPGs) to describe the prevalence of germline pathogenic/likely pathogenic variants (GPVs). Subsequent testing of a subset of tumours for loss of heterozygosity (LOH) evaluation was performed to investigate the clinical and molecular significance of these variants. RESULTS: GPVs were detected in 21.5% (38/177) of the patients (15.8% in children and 21.6% in adolescents and young adults), with dominant CPGs being altered in 15.2% overall. These variants were found in genes previously associated with the risk of developing sarcomas (TP53, RB1, NF1, EXT1/2) but also in genes where that risk is still emerging/limited (ERCC2, TSC2 and BRCA2) or unknown (PALB2, RAD50, FANCM and others). The detection rates of GPVs varied from 0% to 33% across sarcoma subtypes and GPV carriers were more likely to present more than one primary tumour than non-carriers (21.1%×6.5%; p=0.012). Loss of the wild-type allele was detected in 48% of tumours from GPV carriers, mostly in genes definitively associated with sarcoma risk. CONCLUSION: Our findings reveal that a high proportion of young patients with sarcomas presented a GPV in a CPG, underscoring the urgency of establishing appropriate genetic screening strategies for these individuals and their families.

A remote, fully oriented personalized program of physical exercise for women in follow-up after breast cancer treatment improves body composition and physical fitness.

This study aimed to evaluate the efficacy of an individualized remote exercise program on the improvement of body composition and physical fitness of a heterogeneous group of patients who completed breast cancer treatment. This prospective study included 107 women aged 18 to 60, shortly after curative treatment for localized breast cancer, at the Erasto Gaertner Cancer Hospital (HEG) in Curitiba, PR, Brazil. Body composition, maximal oxygen consumption, and muscle resistance were evaluated after nine months of intervention while considering adherence to the program, level of physical activity, presence of binge eating disorder, tumor classification, and treatment type. Seventy-eight women (72.8%) adhered to the training program. Adherent participants showed significant changes in body mass ([-4.3 â€‹± â€‹3.6] kg; p â€‹< â€‹0.000 1), body mass index ([-1.6 â€‹± â€‹1.5] kg·m-2; p â€‹< â€‹0.000 1), body fat (-3.4% â€‹± â€‹3.1%; p â€‹< â€‹0.000 1), maximal oxygen consumption ([7.5 â€‹± â€‹2.0] ml·kg-1·min-1); p â€‹< â€‹0.000 1), and abdominal resistance ([11.2 â€‹± â€‹2.8] reps; p â€‹< â€‹0.000 1). In contrast, these variables did not change significantly in the non-adherent group. Among the adherent participants, those subclassified in the severe binge group showed a more noticeable reduction in body mass, body mass index, and body fat (p â€‹< â€‹0.05) than those in the non-binge group. Individualized remotely-guided physical exercise programs can improve the body composition and physical fitness of women undergoing post-breast cancer surveillance, regardless of pathological history or treatment.

Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. METHODS: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. RESULTS: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574). CONCLUSIONS: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.

Evaluation of the response rate to neoadjuvant chemoradiotherapy in patients with rectal adenocarcinoma: a retrospective long-term study in two terciary reference centers

Objectives: To evaluate the complete response (CR) rate and surgeries performed in patients with rectal adenocarcinoma who underwent neoadjuvant therapy (NT) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Hospital São Paulo, in Ribeirão Preto, from January 2007 to December 2017. Methods: We evaluated 166 medical records of patients with locally advanced rectal adenocarcinoma (T3, T4 or N+) who underwent NT. The regimen consisted of performing conventional (2D) or conformational (three-dimensional-3D/ radiotherapy with modulated intensity - IMRT) at a dose of 45-50.4Gy associated with capecitabine 1650mg/m2 or 5-fluorouracil (5FU) and leucovorin (LV). The following variables were analyzed: gender, age, pretreatment stage, radiotherapy, CR index, local and distant recurrence rates. Surgical treatment and complications were also evaluated. Results: The CR index was 28.3%. Patients treated with 3D/IMRT radiotherapy had a higher rate of CR (36.3% x 4.8%; p < 0.001), higher rates of clinical follow-up (21% x 0%; p < 0.001), lower surgery rates (79% x 100%; p < 0.001), higher rates of transanal resection (37.1% x 9.5%; p = 0.001), lower rates of abdominal rectosigmoidectomy (25.8% x 50%; p = 0.007) and lower rates of abdominoperineal resection of the rectum (16.1% x 40.5%; p = 0.002), when compared to patients treated with 2D radiotherapy. Conclusion Modern radiotherapy techniques such as 3D conformal and IMRT, by offering greater adequacy and precision of treatment, could result in better local control and less toxicity in organs at risk, enabling organ preservation strategies and less invasive approaches in selected cases. (AU)

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology.

INTRODUCTION: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. PURPOSE: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. METHODS: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. RESULTS: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. CONCLUSIONS: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation / Uso de drogas psicotrópicas e sintomas sugestivos de depressão associados à metilação do DNA do NR3C1

Introduction: Psychiatric disorders have become a global problem that leads millions of people to use psychotropic medications, especially benzodiazepines. The effects of these substances are widely known regarding tolerance and chemical dependence, however, from epigenetics perspective, there are still little known.Objective: To evaluate the association between psychotropic drug use, NR3C1 gene methylation and its relation with symptoms suggestive of depression in adult individuals assisted in the public health system.Methods: 385 adult volunteers (20-59 years) users of the Brazilian Unified Health System were recruited to evaluate socioeconomic, health, lifestyle conditions in a cross sectional study. BDI-II evaluated symptoms suggestive of depression and pyrosequencing evaluated NR3C1 DNA methylation. Bivariate and multivariate Poisson regression model with robust variance (p < 0.05) evaluated the association between psychotropic drug use and NR3C1 gene methylation.Results: Specific depressive symptoms such as irritability, insomnia and fatigability were associated with psychotropic drug use. Symptoms of past failure, indecision and loss of appetite were associated with hypermethylation patterns in CpGs 40 to 47 of NR3C1 gene. Moreover, psychotropic drug use is associated with 50% reduction in NR3C1 gene methylation, through model adjusted with socioeconomic, health and lifestyle confounding variables.Conclusions: Psychotropic drug use and depressive symptoms was associated with changes in NR3C1 DNA methylation. In this context, epigenetic modification resulting from psychotropic drug use and depressive symptoms could be considered, mainly in population studies with epigenetic evaluation, where these factors may be influencing the findings of future studies.

Introdução: os distúrbios psiquiátricos tornaram-se um problema global que leva milhões de pessoas ao uso de medicamentos psicotrópicos. Os efeitos dessas substâncias são amplamente conhecidos quanto à tolerância e dependência química, porém, do ponto de vista epigenético, ainda são pouco conhecidos.Objetivos: avaliar a associação entre o uso de drogas psicotrópicas, metilação do gene NR3C1 e sua relação com sintomas sugestivos de depressão em indivíduos entre 20 a 59 anos usuários da rede pública de saúde.Método: 385 voluntários de 20-59 anos, usuários do Sistema Único de Saúde brasileiro foram recrutados para avaliação das condições socioeconômicas, de saúde e de estilo de vida em estudo transversal. O BDI-II avaliou sintomas sugestivos de depressão e o pirosequenciamento avaliou a metilação do DNA de NR3C1. Modelo de regressão de Poisson bivariado e multivariado com variância robusta (p < 0,05) avaliou a associação entre o uso de drogas psicotrópicas e metilação do gene NR3C1.Resultados: sintomas depressivos específicos como irritabilidade, insônia e fadiga foram associados ao uso de medicamentos psicotrópicos. Sintomas de fracasso passado, indecisão e perda de apetite foram associados a padrões de hipermetilação nos CpGs 40 a 47 do gene NR3C1. Além disso, o uso de psicofármacos está associado à redução de 50% na metilação do gene NR3C1, por meio de modelo ajustado com variáveis de confusão socioeconômicas, de saúde e estilo de vida.Conclusão: o uso de drogas psicotrópicas e sintomas específicos depressivos foram associados a alterações na metilação do DNA de NR3C1.