Imbalance of airway proteases and antiproteases has been implicated in diseases such as COPD and environmental exposures including cigarette smoke and ozone. To initiate infection, endogenous proteases are commandeered by respiratory viruses upon encountering the airway epithelium. The airway proteolytic environment likely contains redundant antiproteases and proteases with diverse catalytic mechanisms, however a proteomic profile of these enzymes and inhibitors in airway samples has not been reported. The objective of this study was to first profile extracellular proteases and antiproteases using human airway epithelial cell cultures and ex vivo nasal epithelial lining fluid (NELF) samples. Secondly, we present an optimized method for probing the proteolytic environment of airway surface liquid samples (in vitro and ex vivo) using fluorogenic peptides modeling the cleavage sites of respiratory viruses. We detected 48 proteases in the apical wash of cultured human nasal epithelial cells (HNECs) (n=6) and 57 in NELF (n=13) samples from healthy human subjects using mass-spectrometry based proteomics. Additionally, we detected 29 and 48 antiproteases in the HNEC apical washes and NELF, respectively. We observed large interindividual variability in rate of cleavage of an Influenza H1 peptide in the ex vivo clinical samples. Since protease and antiprotease levels have been found to be altered in the airways of smokers, we compared proteolytic cleavage in ex vivo nasal lavage samples from male/female smokers and non-smokers. There was a statistically significant increase in proteolysis of Influenza H1 in NLF from male smokers compared to female smokers. Furthermore, we measured cleavage of the S1/S2 site of SARS-CoV, SARS-CoV-2, and SARS-CoV-2 Delta peptides in various airway samples, suggesting the method could be used for other viruses of public health relevance. This assay presents a direct and efficient method of evaluating the proteolytic environment of human airway samples in assessment of therapeutic treatment, exposure, or underlying disease.

There is limited evidence on the outcomes and safety of mechanical thrombectomy (MT) among patients with acute ischemic stroke (AIS) in the context of cardiac diseases. Our study reviews MT in AIS within the context of cardiac diseases, aiming to identify existing and emerging needs and gaps. PubMed and Scopus were searched until December 31, 2023, using a combination of cardiological diseases and "mechanical thrombectomy" or "endovascular treatment" as keywords. Study design included case reports/series, observational studies, randomized clinical trials, and meta-analyses/systematic reviews. We identified 943 articles, of which 130 were included in the review. Results were categorized according to the cardiac conditions. MT shows significant benefits in patients with atrial fibrillation (n=139) but lacks data for stroke occurring after percutaneous coronary intervention (n=2) or transcatheter aortic valve implantation (n=5). MT is beneficial in AIS attributable to infective endocarditis (n=34), although functional benefit may be limited. Controversy surrounds the functional outcomes and mortality of patients with AIS with heart failure undergoing MT (n=11). Despite technical challenges, MT appears feasible in aortic dissection cases (n=4), and in patients with left ventricular assist device or total artificial heart (n=10). Data on AIS attributable to congenital heart disease (n=4) primarily focus on pediatric cases requiring technical modifications. Treatment outcomes of MT in patients with cardiac tumors (n=8) vary because of clot consistency differences. After cardiac surgery stroke, MT may improve outcomes with early intervention (n=13). Available data outline the feasibility of MT in patients with AIS attributable to large-vessel occlusion in the context of cardiac diseases.

BACKGROUND: Due to the declining mortality rates of breast carcinoma and the rising incidence of risk-reducing mastectomies, enhancing the quality of life after breast reconstructions has become an increasingly important goal. The advantages of lightweight breast implants (B-Lite®) may significantly contribute to achieving this objective. This study aims to investigate whether lightweight implants are suitable for patients undergoing breast reconstruction and could improve the quality of life in comparison to conventional implants. METHODS: In this study, we retrospectively analyzed 48 patients (38 implants in each group) who underwent implant-based breast reconstruction with either B-Lite® or conventional breast implants between 2019 and 2022 at the University Center for Plastic Surgery in Regensburg. As part of the postoperative follow-up, a clinical examination and a survey using the Breast-Q® questionnaire were conducted to evaluate the postoperative quality of life. RESULTS: The implants used were similar in weight and shape. On average, the B-Lite® implants had a higher implant volume and patients in this group had a slightly higher BMI. Patients who received B-Lite® implants showed a significantly better result regarding the sensation of sensitivity in the surgical area and the scar formation also appeared to be more favorable. However, patients with B-Lite® implants perceived their implants as more uncomfortable than those with conventional breast implants. In other terms concerning quality of life, both groups appeared similar. CONCLUSION: In summary, there are confounding factors that could influence the outcome of some aspects in this study, which could not be avoided due to the retrospective study design and the temporary suspension of B-Lite implants. Nevertheless, as the first of its kind, this study demonstrated that B-Lite implants could also be suitable for usage in breast reconstructions, thus providing an important foundation for further prospective studies to build upon.

BACKGROUND: Thyroid cancer, a leading type of endocrine cancer, accounts for 3-4% of all cancer diagnoses. This study aims to analyse and compare thyroid cancer patterns in China and the Group twenty (G20) countries, and predict these trend for the upcoming two decades. METHODS: This observational longitudinal study utilised data from the Global Burden of Disease (GBD) study 2019. We used metrics including incidence, mortality, mortality-incidence ratio (MIR), age-standardised rate (ASR) and average annual percent change (AAPC) to examine thyroid cancer trends. Joinpoint regression analysis was used to identify periods manifesting notable changes. The association between sociodemographic index (SDI) and AAPC were investigated. The autoregressive integrated moving average (ARIMA) model was used to predict thyroid cancer trends from 2020 to 2040. RESULTS: From 1990 to 2019, thyroid cancer incidence cases in China increased by 289.6%, with a higher AAPC of age-standardised incidence rate (ASIR) in men. Contrastingly, the G20 demonstrated a smaller increase, particularly among women over 50. Despite the overall age-standardised mortality rate (ASMR) was higher in the G20, the increase in mortality was less pronounced than in China. Age-standardised incidence rate increased across all age groups and genders, with a notable rise among men aged 15-49. ASMR decreased in specific age groups and genders, especially among women. Conversely, the ASMR significantly increased in group aged over 70. The MIR exhibited a declining trend, but this decrease was less noticeable in men and the group aged over 70. Joinpoint analysis pinpointed significant shifts in overall ASIR and ASMR, with the most pronounced increase in ASIR during 2003-2011 in China and 2003-2010 in the G20. Predictions suggested a continual ASIR uptrend, especially in the 50-69 age group, coupled with a predicted ASMR downturn among the elderly by 2040. Moreover, the proportion of thyroid cancer deaths attributable to high body mass index (BMI) escalated, with significant increase in Saudi Arabia and a rise to 7.4% in China in 2019. CONCLUSIONS: Thyroid cancer cases in incidence and mortality are escalating in both China and the G20. The increasing trend may be attributed to factors beyond overdiagnosis, including environmental and genetic factors. These findings emphasise the necessity for augmenting prevention, control, and treatment strategies. They also highlight the significance of international collaboration in addressing the global challenge posed by thyroid cancer.

Background The increasing incidence of type 2 diabetes (T2D) in India underscores the pressing need for effective management strategies. Meeting the American Diabetes Association (ADA) ABC targets for diabetes (glycated hemoglobin (HbA1c), blood pressure, and serum low-density lipoprotein cholesterol (LDL-C)) is crucial for effectively managing T2D, as it reflects the optimal control of key metabolic parameters. Insulin resistance (IR) and impaired beta cell function (BCF) have been found to have a significant impact on glycemic control, lipid metabolism, and hypertension, contributing to the complex cardiovascular risk profile of patients with T2D. This study aimed to explore the association between ABC targets for diabetes, IR, BCF, and dyslipidemia in a cross-sectional cohort of T2D patients. Methods This retrospective study examined data from 681 T2D patients with comorbid hypertension and dyslipidemia. The patients were part of a one-year online lifestyle intervention program for diabetes management at the Freedom from Diabetes Clinic in Pune, India, between January 2021 and December 2022. Baseline data (at the time of enrollment in the program) on medical history and anthropometric and biochemical parameters were retrospectively extracted from medical records and used to assess ABC targets and other clinical parameters. The ABC targets for diabetes include three goals: an HbA1c level of less than 7.0%, a blood pressure level of less than 140/90 mmHg, and an LDL-C level of less than 100 mg/dL. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of Beta Cell Function (HOMA-B), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated using standard formulas. Results Cross-sectional analysis at baseline showed that 152 (22.3%) participants met all three ABC targets, 306 (45.0%) and 183 (26.8%) participants met two or one targets, respectively, and 40 (5.9%) did not meet any of the ABC targets. Participants meeting all three targets showed significantly lower IR, higher sensitivity (HOMA-IR, median 2.1; QUICKI, median 0.34), higher BCF (HOMA-B, median 62.9), and healthier lipid profiles (mg/dL) (total cholesterol, median 126; triglycerides, median 114; and non-high-density lipoprotein (HDL), median 84) than those who did not meet any of the ABC targets (HOMA-IR, median 3.4; QUICKI, median 0.31; HOMA-B, median 31.7; total cholesterol, median 221; triglycerides, median 187; and non-HDL, median 182) (p < 0.01). A significant association was observed between lower BMI (< 25 kg/m2), lower IR (HOMA-IR <2.5), and meeting all three ABC targets (p < 0.01). No significant association was observed between the duration of diabetes and ABC target status (p > 0.1). Lower IR was identified as a predictor of achievement of all three ABC targets (p < 0.01). Conclusion This study highlights the significance of meeting ABC targets for diabetes in relation to not only a better lipid profile but also lower IR and higher BCF. These preliminary findings provide novel insights into the interplay between IR, BCF, dyslipidemia, and meeting ABC targets in an Indian T2D population. These findings highlight the need for effective diabetes management strategies and improved patient outcomes, considering factors such as BMI and IR indices.

BACKGROUND AND OBJECTIVES: Distal symmetric polyneuropathy (DSP) is a disabling, often painful condition associated with falls and reduced quality of life. Non-Hispanic Black people and people with low income are underrepresented in existing DSP studies; therefore, it is unknown whether data accurately reflect the prevalence, risk factors, and burden of disease in these populations. METHODS: Patients older than 40 years presenting to an outpatient internal medicine clinic predominantly serving Medicaid patients in Flint, Michigan, were enrolled in a cross-sectional study. Demographics, clinical characteristics, including medication use, anthropomorphic measurements, fasting lipids, and hemoglobin A1c were collected. DSP was defined using the modified Toronto Clinical Neuropathy Score (mTCNS). Multivariable logistic regression was performed to model DSP and undiagnosed DSP as a function of potential risk factors age, metabolic syndrome, and race. DSP burden was measured using Peripheral Neuropathy Quality of Life Instrument-97. RESULTS: Two hundred participants were enrolled, and 169 (85%) completed all data collection. The population was 55% female of mean age (SD) 58.2 years (10.4) and 69% non-Hispanic Black. Among the population, 50% had diabetes, 67% had metabolic syndrome, and 47% had a household income <$20,000. DSP was present in 73% of the population, of which 75% were previously undiagnosed. Neuropathic pain was documented in 57% of participants with DSP. DSP based on mTCNS criteria was associated with older age (odds ratio [OR] 1.1 [95% confidence interval (CI) 1.03-1.2]) and metabolic syndrome (OR 4.4 [1.1-18.1]). Non-Hispanic Black participants had lower odds of DSP (OR 0.1 [0.01-0.4]) than non-Hispanic White and Hispanic participants. DSP burden was high, including increased pain, health-related worry, and poorer quality of life (all p < 0.001). DISCUSSION: DSP is extremely common and often underrecognized in this predominantly non-Hispanic Black, low-income population and leads to substantial disease burden. Metabolic syndrome is a highly prevalent, modifiable risk factor in this population that should be managed to lower DSP prevalence.

BACKGROUND: Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses. METHODS: Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence. RESULTS: Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9-5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02-1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44-3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26-3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86-8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001). CONCLUSIONS: Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.

The aim was to investigate the independent risk factors for lower extremity deep vein thrombosis (DVT) after total knee arthroplasty, and to establish a nomogram prediction model accordingly. Data were collected from total knee replacement patients from January 2022 to December 2023 in our hospital. Unifactorial and multifactorial logistic regression analyses were used to determine the independent risk factors for lower extremity DVT after total knee arthroplasty and to establish the corresponding nomogram. The receiver operating characteristic curves were plotted and the area under the curve was calculated, and the calibration curves and decision curves were plotted to evaluate the model performance. A total of 652 patients with total knee arthroplasty were included in the study, and 142 patients after total knee arthroplasty developed deep veins in the lower extremities, with an incidence rate of 21.78%. After univariate and multivariate logistic regression analyses, a total of 5 variables were identified as independent risk factors for lower extremity DVT after total knee arthroplasty: age > 60 years (OR: 1.70; 95% CI: 1.23-3.91), obesity (OR: 1.51; 95% CI: 1.10-1.96), diabetes mellitus (OR: 1.80; 95% CI: 1.23-2.46), D-dimer > 0.5 mg/L (OR: 1.47; 95% CI: 1.07-1.78), and prolonged postoperative bed rest (OR: 1.64; 95% CI: 1.15-3.44). the nomogram constructed in this study for lower extremity DVT after total knee arthroplasty has good predictive accuracy, which helps physicians to intervene in advance in patients at high risk of lower extremity DVT after total knee arthroplasty.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.

INTRODUCTION: Bariatric surgery is established as a possibility for the treatment of obesity, allowing weight reduction and remission of obesity comorbidities. Reported suboptimal clinical response rates are as high as 30-60% (insufficient weight loss or gain, defined as BMI greater than 35 kg/m2 or excess weight loss less than 50%). Proximal jejuno-ileal bypass (PJIBP) is a promising option when re-intervention is required. OBJECTIVES: To describe the standardization of a proprietary technique of modified PJIBP as a management procedure in patients with post-gastric bypass recurrent weight gain or insufficient post-intervention weight loss. METHODS: This study evaluated a case series of 10 Latin American patients requiring post-bariatric re-intervention, between February 2018 and 2023, in a single-metabolic surgery center in Cali-Colombia. RESULTS: Median age was 45 years (26-70 RIC), 60% female, and 40% male. Mean BMI at conversion was 36.7 kg/m2 (6.4 SD). Median follow-up was 22 months (RIC 16-30). Mean percentage of excess weight lost was 78% (22.4 SD). One hundred percent achieved glycemia control, only one patient persisted with dyslipidemia, and no patient presented hypoalbuminemia. At the end of follow-up, 100% received vitamin supplementation. CONCLUSION: PJIBP could be an effective procedure, associated with positive results in relation to weight loss and resolution of obesity comorbidities. Deficiencies of fat-soluble vitamins and protein malnutrition represent the main concern in the long term, so multidisciplinary management and continuous follow-up are required.