Clinical and Microbiological Characteristics of Febrile Neutropenia During Induction Chemotherapy in Adults With Acute Leukemia.

BACKGROUND: Few studies regarding infectious causes of febrile neutropenia (FN) in Mexico are available. AIMS: We aimed to describe clinical and microbiological characteristics of FN episodes during induction chemotherapy in adults with acute leukemia. METHODS AND RESULTS: This retrospective cohort from a Mexican tertiary care center included adults with newly diagnosed acute leukemia between January 2014, and December 2018. Clinical and microbiological characteristics were summarized using descriptive statistics. Univariate analyses for associations between clinical characteristics and FN and/or death were made; logistic regression analysis was performed to assess relationships with FN. Kaplan-Meier survival estimates were modeled for antimicrobial prophylaxis and FN. Ninety-five patients were included. Median age was 28 (IQR 20-43), 49 (52%) were males, and 74 (78%) developed FN (74/95). Among these, 98% had an identified source of infection (73/74) and 65% had >1. Common infections were urinary tract infection (24%), bacterial sinusitis (20%), and bacterial pneumonia (19%). Gram-negatives were the most frequently isolated microorganisms (69%), followed by Gram-positives (21%), and fungi (9%). Antimicrobial prophylaxis was inversely associated with FN (aOR = 0.07, CI 0.008-0.060, p = 0.02). Invasive fungal diseases were associated with 30-day mortality (aOR = 9.46, 95% CI 1.66-54.05). CONCLUSION: Infections caused 98% of the FN episodes. Gram-negative bacteria are the most common pathogens.

Light exposure of tetra-cationic porphyrins containing peripheral Pd(II)-bipyridyl complexes and the induced effects on purified DNA molecule, fibroblast and melanoma cell lines.

Photodynamic therapy (PDT) combines a light source, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) for treating diseases. In this study, we evaluated two meso-tetra-pyridyl porphyrins with [Pd(bpy)Cl]+, namely 3-PdTPyP and 4-PdTPyP, as PS for PDT application. DNA interaction was assessed by spectroscopic measurements (UV-Vis and fluorescence emission), viscosity analysis, and molecular docking simulations. The results indicate that Pd(II)-porphyrins do not intercalate into DNA, suggesting that the minor groove is the primary interaction site, mainly through van der Waals forces. These metalloporphyrins effectively induced nitrogenous bases oxidation, particularly in purines, after white light irradiation. The induced DNA lesions were able to inactivate plasmid DNA metabolism (DNA replication and transcription) in a bacterial model. 3-PdTPyP and 4-PdTPyP significantly decreased the viability of treated melanoma cell lines (A375 and B16-F10), demonstrating that melanoma cell lines were more sensitive to these Pd(II)-porphyrins than the fibroblast cell line (L929). Moreover, 3-PdTPyP was more photototoxic to A375 cells (IC50 = 0.43 µM), whereas 4-PdTPyP was more photototoxic to B16-F10 cells (IC50 = 0.51 µM). These findings suggest that these porphyrins are promising PS for future PDT research focused on skin cancer.

Granular Cell Tumor Initially Masquerading as Cellulitis.

Granular cell tumor (GCT), a rare Schwann cell-derived lesion, typically manifests as a benign skin or soft tissue growth. We report a case of GCT mimicking cellulitis on a woman's foot at first presentation. Despite initial misdiagnosis, histological examination confirmed GCT, guiding successful excision and reconstruction. Our case underscores the importance of considering granular cell tumors in atypical presentations and highlights the role of histological evaluation in accurate diagnosis and management.

Histoplasmosis Beyond Human Immunodeficiency Virus (HIV): Clinical Characteristics and Outcomes in a Non-HIV Population.

Histoplasmosis is an endemic and invasive mycosis caused by Histoplasma capsulatum. We conducted a retrospective study comparing immunosuppressed patients without human immunodeficiency virus (HIV) with a historical cohort of people with HIV and histoplasmosis. We included 199 patients with proven or probable histoplasmosis, of which 25.1% were people without HIV. Diabetes mellitus, chronic kidney disease, hematologic neoplasms, rheumatologic diseases, and transplantations were more frequent among people without HIV (P < .01). Forty-four percent of immunocompromised patients without HIV died within the first 6-week period following their diagnosis. A high suspicion index for histoplasmosis should be kept in immunosuppressed patients.

Combat-related Wartenberg Syndrome Due to Penetrating Shrapnel Injury: A Case Report.

Wartenberg syndrome, also known as Cheiralgia paresthetica, is an uncommon neuropathy affecting the superficial branch of the radial nerve. Typically caused by external compression, it manifests as paresthesia or pain in the radial side of the hand. We present a case of Wartenberg syndrome resulting from combat shrapnel injury, illustrating an uncommon etiology. A 21-year-old soldier was presented with allodynia and paresthesia after a shrapnel explosion, with positive clinical findings and radiographic evidence supporting the diagnosis. Nonoperative management led to significant improvement, highlighting the importance of conservative treatment in such cases. This report underscores the significance of considering unconventional causes in nerve entrapment syndromes post combat trauma, emphasizing adherence to established therapeutic guidelines.

Identification and structural characterization of small molecule inhibitors of PINK1.

Mutations in PINK1 and Parkin cause early-onset Parkinson's Disease (PD). PINK1 is a kinase which functions as a mitochondrial damage sensor and initiates mitochondrial quality control by accumulating on the damaged organelle. There, it phosphorylates ubiquitin, which in turn recruits and activates Parkin, an E3 ubiquitin ligase. Ubiquitylation of mitochondrial proteins leads to the autophagic degradation of the damaged organelle. Pharmacological modulation of PINK1 constitutes an appealing avenue to study its physiological function and develop therapeutics. In this study, we used a thermal shift assay with insect PINK1 to identify small molecules that inhibit ATP hydrolysis and ubiquitin phosphorylation. PRT062607, an SYK inhibitor, is the most potent inhibitor in our screen and inhibits both insect and human PINK1, with an IC50 in the 0.5-3 µM range in HeLa cells and dopaminergic neurons. The crystal structures of insect PINK1 bound to PRT062607 or CYC116 reveal how the compounds interact with the ATP-binding pocket. PRT062607 notably engages with the catalytic aspartate and causes a destabilization of insert-2 at the autophosphorylation dimer interface. While PRT062607 is not selective for PINK1, it provides a scaffold for the development of more selective and potent inhibitors of PINK1 that could be used as chemical probes.

Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Robotic-Assisted Stereoelectroencephalography: A Systematic Review and Meta-Analysis of Safety, Outcomes, and Precision in Refractory Epilepsy Patients.

Robotic assistance in stereoelectroencephalography (SEEG) holds promising potential for enhancing accuracy, efficiency, and safety during electrode placement and surgical procedures. This systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration, delves into the latest advancements and implications of robotic systems in SEEG, while meticulously evaluating outcomes and safety measures. Among 855 patients suffering from medication-refractory epilepsy who underwent SEEG in 29 studies, averaging 24.6 years in age, the most prevalent robots employed were robotic surgical assistant (ROSA) (450 patients), Neuromate (207), Sinovation (140), and ISys1 (58). A total of 8,184 electrodes were successfully implanted, with an average operative time of 157.2 minutes per procedure and 15.1 minutes per electrode, resulting in an overall mean operative time of 157.7 minutes across all studies. Notably, the mean target point error (TPE) stood at 2.13 mm, the mean entry point error (EPE) at 1.48 mm, and postoperative complications occurred in 7.69% of robotically assisted (RA) SEEG cases (60), with 85% of these complications being asymptomatic. This comprehensive analysis underscores the safety and efficacy of RA-SEEG in patients with medication-refractory epilepsy, characterized by low complication rates, reduced operative time, and precise electrode placement, supporting its widespread adoption in clinical practice, with no discernible differences noted among the various robotic systems.

A nonequilibrium allosteric model for receptor-kinase complexes: The role of energy dissipation in chemotaxis signaling.

The Escherichia coli chemotaxis signaling pathway has served as a model system for the adaptive sensing of environmental signals by large protein complexes. The chemoreceptors control the kinase activity of CheA in response to the extracellular ligand concentration and adapt across a wide concentration range by undergoing methylation and demethylation. Methylation shifts the kinase response curve by orders of magnitude in ligand concentration while incurring a much smaller change in the ligand binding curve. Here, we show that the disproportionate shift in binding and kinase response is inconsistent with equilibrium allosteric models. To resolve this inconsistency, we present a nonequilibrium allosteric model that explicitly includes the dissipative reaction cycles driven by adenosine triphosphate (ATP) hydrolysis. The model successfully explains all existing joint measurements of ligand binding, receptor conformation, and kinase activity for both aspartate and serine receptors. Our results suggest that the receptor complex acts as an enzyme: Receptor methylation modulates the ON-state kinetics of the kinase (e.g., phosphorylation rate), while ligand binding controls the equilibrium balance between kinase ON/OFF states. Furthermore, sufficient energy dissipation is responsible for maintaining and enhancing the sensitivity range and amplitude of the kinase response. We demonstrate that the nonequilibrium allosteric model is broadly applicable to other sensor-kinase systems by successfully fitting previously unexplained data from the DosP bacterial oxygen-sensing system. Overall, this work provides a nonequilibrium physics perspective on cooperative sensing by large protein complexes and opens up research directions for understanding their microscopic mechanisms through simultaneous measurements and modeling of ligand binding and downstream responses.

Systematic literature review of cold-formed steel at elevated temperature scenario.

Cold-formed steels (CFS) or light gauge steels (LGS) are steel sections created through processes without heat application, such as roll forming or press-braking. In the past few decades, the utilization of CFS as a structural material has expanded due to its advantages over the other materials used in the construction industry, consequently increasing the number of studies conducted by many researchers. CFS studies have focused on many research areas, including designing, and analyzing members and systems, connections, sustainability, residual stresses, and post-fire data. As a result, several authors have also conducted a literature review involving these areas. However, a literature review for more recent studies involving elevated temperature exposure of CFS has not been conducted. This paper seeks to compile and review the recent publications regarding CFS behavior and performance at high temperatures events. Sixty-nine (69) journal articles published from 2017 to 2023 were retrieved from the Scopus database and systematically reviewed through text mining with the aid of VOS Viewer. Prior studies utilizing finite element analysis and experimental methods to investigate the performance at elevated temperature events of varying CFS sections, systems, and steel grades have been summarized. In addition, this paper also briefly discussed the findings of the recent research works involving member connections of CFS. Key points from the literature review have been emphasized such as the outcome of experimental and numerical validation of existing design rules from different codes such as American Iron and Steel Institute (AISI), Eurocodes, and Australian codes which could vary depending on the CFS section and steel grades. Important points of previous studies regarding the CFS walls, insulations, and screwed connections have also been noted in this paper. Based on the review, research gaps in the prior studies involving elevated temperature exposure of CFS have been identified, such as lack of CFS investigation under fatigue and cyclic loading. These were then recommended as future direction and concentration of CFS at elevated temperatures research works.

Estimating mortality in women with triple-negative breast cancer: The 'ESTIMATE triple-negative' tool.

PURPOSE: Triple-negative breast cancer (TNBC) is associated with a high risk of breast cancer-specific mortality (BCSM). Estimating the risk of BCSM and non-BCSM in TNBC would aid clinical decision-making. We developed the tool 'ESTIMATE-TN', to assess BCSM, non-BCSM, and all-cause mortality in non-metastatic TNBC. METHODS: Using Surveillance, Epidemiology, and End Results (SEER), we created an interactive tool that provides a nonparametric estimate of the cumulative risk of BCSM and non-BCSM between years 0 and 7 from diagnosis, accounting for baseline clinical and pathologic variables, using Gray's subdistribution method. RESULTS: We included 37,293 women with TNBC diagnosed during 2010-2017. Most patients were White (71.9%) and aged 50-69 years (51.3%). Most tumour characteristics were high-grade (78.6%), T2 (42.4%), and N0 (69.5%). ESTIMATE-TN allows to input patient and tumour characteristics, and the preferred timeframe. For example, patients aged 50-59 years with a new diagnosis of T2, N1, high-grade TNBC have a risk of BCSM at 7 years of 30.8% (95% confidence interval [CI]: 26.3-35.4%) and a risk of non-BCSM over the same period of 2.8% (95% CI: 1.3-4.3%). After 3 years from initial diagnosis, the residual cumulative risks of BCSM and non-BCSM at 7 years are 17.4% (95% CI: 12.6-22.2%) and 1.1% (95% CI: 0-2.5%), respectively. CONCLUSIONS: ESTIMATE-TN is an interactive tool for TNBC that can be used to integrate population-based risks of BCSM and non-BCSM based on patient and tumour characteristics, facilitating our understanding of competing risks of death, which can aid clinical decision-making.

Traumatic Brain Injury in the Setting of Fahr Syndrome.

Fahr syndrome, or bilateral striatopallidodentate calcinosis, is a rare syndrome that can confound interpretation of traumatic brain injury seen on computed tomography of the head (CTH). Understanding that this syndrome presents with diffuse calcified lesions will assist clinicians unfamiliar with Fahr syndrome when evaluating diffuse hyperdensities seen on CTH in the setting of trauma between traumatic acute blood versus calcification. We present a unique image that demonstrates how a traumatic brain injury patient can present with traumatic acute hemorrhage and Fahr syndrome. We highlight 2 methods within the CTH images that can be used to assist in these diagnoses, which will better inform neurosurgeons and other clinicians when encountering this unique and rare presentation for the first time.

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study.

Background: MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD). Methods: We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD. Results: Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005-1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456-8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229-8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133-6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, p = 0.009). Conclusions: Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation. Trial registration: www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.

Photophysical, photobiological, and biomolecule-binding properties of new tri-cationic meso-tri(2-thienyl)corroles with Pt(II) and Pd(II) polypyridyl derivatives.

We report the synthesis and characterization of new tri-cationic corrole derivatives, containing Pt(II) or Pd(II) complexes attached at the peripheral position of thienyl moieties. Corrole derivatives were characterized through microanalysis, electrochemical, spectrometry and spectroscopy analysis. Singlet and triplet excited-states are investigated by photophysical/theoretical calculation methods and photobiological parameters were also evaluated spectroscopic techniques (UV-Vis and EPR). Also, the binding capacity of each corrole derivative with nucleic acids (DNA) and human serum albumin (HSA) was determined by UV-Vis, steady-state, and time-resolved fluorescence spectroscopy, combined with molecular docking analysis. Moreover, the new corroles containing peripheral complexes improve their interactions with biomacromolecules, generate reactive oxygen species under light source irradiation studied and has potential for application in photodynamic therapeutic processes.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

Survival in male breast cancer over the past 3 decades.

BACKGROUND: Breast cancer mortality in women has declined statistically significantly over the past several years. In men, it is unclear whether survival has changed over time. We evaluated changes in breast cancer-specific survival (BCSS) and overall survival (OS) in male breast cancer over the past 3 decades. METHODS: We evaluated men diagnosed with breast cancer between 1988 and 2017, reported in the Surveillance, Epidemiology, and End Results registry. Patients were categorized into 3 groups by year of diagnosis: 1988-1997, 1998-2007, and 2008-2017. BCSS and OS were estimated by Kaplan-Meier, and differences between groups were compared by log-rank test. Multivariable Cox regression evaluated the independent association of year of diagnosis with BCSS and OS. All tests were 2-sided. RESULTS: We included 8481 men. Overall, BCSS at 5 years was 83.69%, 83.78%, and 84.41% in groups 1988-1997, 1998-2007, and 2008-2017, respectively (P = .86). There was no statistically significant difference in BCSS between the 3 groups within each stage of disease. Among all patients, OS at 5 years was 64.61%, 67.31%, and 69.05% in groups 1988-1997, 1998-2007, and 2008-2017, respectively (P = .01). In adjusted Cox models, each additional year of diagnosis had no statistically significant association with BCSS (hazard ratio = 1.00, 95% confidence interval = 0.99 to 1.01, P = .75), but there was statistically significant improvement in OS (hazard ratio = 0.99, 95% CI = 0.98 to 0.99, P = .009). CONCLUSIONS: Over the past 3 decades, there has been no statistically significant improvement in BCSS in male breast cancer. Changes in OS over time are consistent with increasing life expectancy. Efforts to improve BCSS in male breast cancer are warranted.

Early Outpatient Treatment With Remdesivir in Patients at High Risk for Severe COVID-19: A Prospective Cohort Study.

Background: Early treatment of coronavirus disease 2019 (COVID-19) with remdesivir in high-risk patients, including those with immunosuppression of different causes, has not been evaluated. The objective of this study was to assess the clinical effectiveness of early remdesivir treatment among patients with mild to moderate COVID-19 at high risk of progression. Methods: This prospective cohort comparative study was conducted in a tertiary referral center in Mexico City. Patients with mild to moderate COVID-19 at high risk for progression were treated with an ambulatory 3-day course of remdesivir. The primary efficacy composite outcome was hospitalization or death at 28 days after symptom onset. A Cox proportional hazards regression model was used to identify associations with the primary outcome. Results: From December 1, 2021, to April 30, 2022, a total of 196 high-risk patients were diagnosed with COVID-19, of whom 126 were included in this study (43%, 54/126, received remdesivir; 57%, 72/126, did not receive remdesivir). Baseline clinical characteristics were similar between groups; autoimmune diseases (39/126), solid organ transplant (31/126), and malignant neoplasms (24/126) were the most common immunocompromising conditions. Diabetes mellitus was strongly associated with the primary outcome in both groups. Prior severe acute respiratory syndrome coronavirus 2 infection or vaccination was not independently associated with COVID-19 progression. Treatment with remdesivir significantly reduced the odds of hospitalization or death (adjusted hazard ratio, 0.16; 95% CI, 0.06-0.44; P < .01). Conclusions: Early outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with Omicron variant COVID-19.

Predictors of poor outcomes in young non-comorbid patients with COVID-19

ABSTRACT Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objective: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV.

Efficacy of neoadjuvant chemotherapy in male breast cancer compared with female breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is standard for many females with breast cancer (FBC). The efficacy of NAC in male breast cancer (MaBC) is unclear. The aim of this study was to compare proportions of pathologic complete response (pCR) between MaBC and FBC by tumor subtype (TS). METHODS: MaBC and FBC treated with NAC between 2010 and 2016, with known TS, were evaluated from the National Cancer Database. Proportions of pCR (ypT0/Tis ypN0) were compared between sexes within TS by Fisher test. Multivariable logistic regression assessed the independent association of sex with pCR. Overall survival (OS) was estimated by Kaplan-Meier. RESULTS: A total of 385 MaBC and 68,065 FBC were included. Median time from initiation of NAC to surgery was 143 days in MaBC and 148 days in FBC. Proportions of pCR in MaBC and FBC by TS were: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-): 4.9% vs 9.7%, p = .01; HR+/HER2+: 16.1% vs 33.6%, p < .001; HR-/HER2+: 44.0% vs 53.2%, p = .42; and HR-/HER2-: 21.4% vs 32.1%, p = .18, respectively. FBC had twice the odds of pCR than MaBC (adjusted odds ratio, 2.0; 95% CI, 1.5-2.8; p < .001). Five-year OS for MaBC with pCR vs not was 90% vs 64.7%; p = .02. Five-year OS for FBC with pCR vs not was 91.9% vs 75.3%; p < .01. CONCLUSIONS: Proportions and odds of pCR to NAC were numerically lower in MaBC compared with FBC for each TS and statistically significant for HR+/HER2- and HR+/HER2+. The independent association of sex with pCR was confirmed in multivariable analysis. pCR is prognostic in both MaBC and FBC.

Estimating long-term mortality in women with hormone receptor-positive breast cancer: The 'ESTIMATE' tool.

PURPOSE: The risk of breast cancer-specific mortality (BCSM) persists for at least 20 years from diagnosis. Estimating the risk of BCSM over this extended period along with competing risks of death would aid clinical decision-making. We aimed to develop an interactive tool called 'ESTIMATE', to explore the Surveillance, Epidemiology, and End Results (SEER) registry to quantify residual risks of BCSM, non-BCSM and all-cause mortality in non-metastatic, hormone receptor (HR)-positive breast cancer patient subgroups at any given time after diagnosis, up to 20 years. METHODS: Using SEER data, we included 264,237 women with invasive, non-metastatic, HR-positive breast cancer diagnosed from 1990 to 2006. We developed a tool that provides a nonparametric estimate of the residual cumulative risk of BCSM and non-BCSM by year 20 after any specified time from initial diagnosis, among patients defined by baseline clinical and pathologic variables, using Gray's subdistribution method. RESULTS: ESTIMATE allows the user to input patient and tumour characteristics and the preferred timeframe. For example, patients in the age group of 40-49 diagnosed with T1cN1, grade II breast cancer who survived 7 years, have a 14% (95% confidence interval [CI]: 11.9%-16.1%) residual cumulative risk of BCSM in the next 13 years, and a 6.4% (95% CI: 4.7%-8.1%) residual cumulative risk of non-BCSM over the same period. CONCLUSIONS: ESTIMATE provides population-based risks of BCSM, non-BCSM and all-cause mortality through 20 years after diagnosis of HR-positive breast cancer, based on patient and tumour characteristics. ESTIMATE can inform discussions about prognosis, a balance between competing risks and aid clinical decision-making.