Venous thromboembolism in benign esophageal surgery patients: potential cost effectiveness of Caprini risk stratification.

BACKGROUND: The Caprini risk assessment model (RAM) stratifies surgical patients for prescription of post-discharge extended heparin prophylaxis to reduce post-operative venous thromboembolism (VTE) events. The average cost for treatment of a VTE event is $15,123. The 30-day post-operative VTE rate after benign esophageal procedures is < 0.8% per the Society of Thoracic Surgeons database. We hypothesized that the financial cost of selective extended prophylaxis in patients undergoing surgery for benign esophageal disease would exceed the cost of treating these rare events and therefore use of risk stratification for extended prophylaxis would not be beneficial. METHODS: All patients undergoing operations for benign esophageal pathology from July 2014 to May 2019 were reviewed. Patients designated as moderate or high risk for VTE were prescribed a 10- or 30-day post-operative course of extended prophylaxis with low-molecular weight heparin (LMWH). VTE and adverse bleeding events were recorded for the 60-day post-operative period. The cost of LMWH was provided by the institution pharmacy. RESULTS: Records from 154 patients were eligible for review. Caprini RAM was used for all patients with the following distribution of risk categories: low = 64.9% (100/154); moderate = 31.8% (49/154); and high = 3.2% (5/154). The average cost of extended prophylaxis at discharge for the moderate-risk group was $121.23, while the high-risk group was $446.46. There were no 60-day VTE or adverse bleeding events recorded. CONCLUSIONS: The majority of patients undergoing surgical therapy were at low risk of post-operative VTE event, with only 35% requiring extended VTE prophylaxis at time of discharge. When compared with the average cost of treatment for a VTE event, the cost of extended prophylaxis per patient in moderate or high-risk groups is substantially lower. In the era of cost-containment, risk stratification and extended prophylaxis may reduce healthcare costs and warrant future investigations.

Prognostic Value of Serum Thyroglobulin Measured at 48 Hours Versus 72 Hours after Second Dose of Recombinant Human Thyrotropin in Surveillance of Well-Differentiated Thyroid Cancer.

OBJECTIVE: The sensitivity of thyroglobulin (Tg) to detect differentiated thyroid cancer recurrence increases with the rise of the thyrotropin level. Since 1998, recombinant human thyrotropin (rhTSH) has been commercially available for this purpose. The traditional protocol for using rhTSH calls for 2 daily injections of rhTSH, followed by the measurement of Tg 72 hours after the second dose. In this study, we compared the performance of rhTSH-stimulated Tg (rhTSH-Tg) obtained at 48 versus 72 hours after the second rhTSH. METHODS: A retrospective chart review of 1088 patients with thyroid cancer was conducted. Two hundred forty-nine rhTSH-Tg, without measurable Tg antibody, were identified, 134 of which were obtained at 48 hours (4-day test) and 115 at 72 hours after the second rhTSH (5-day test). The ability of rhTSH-Tg to identify recurrence or persistence of differentiated thyroid cancer and to predict response to therapy at the end of the study period was compared between the 2 groups. RESULTS: The median duration of follow-up was 8 years. When recurrent/persistent cancer was present based on a combination of unstimulated Tg, imaging and procedures, the ratio of rhTSH-Tg ≥ 1 ng/mL was similar in both groups (P value: .153). The negative predictive value of rhTSH-Tg to predict response to therapy over the long term was 95% or higher in 4-day and 5-day tests. CONCLUSION: Tg measured 48 and 72 hours after the second dose of rhTSH may provide a comparable prognostic value. These results encourage further studies to identify new protocols to obtain rhTSH-Tg.

Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial.

IMPORTANCE: Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown. OBJECTIVE: To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Testosterone's Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012. INTERVENTIONS: One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES: Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life. RESULTS: Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, -0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, -10.8 Agatston units/year; 95% CI, -45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group. CONCLUSIONS AND RELEVANCE: Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00287586.

Current state and novel outlook on prevention and treatment of rising antibiotic resistance in urinary tract infections.

Antibiotic-resistant bacteria are currently an important public health concern posing a serious threat due to their resistance to the current arsenal of antibiotics. Uropathogens Escherichia coli (UPEC), Proteus mirabilis, Klebsiella pneumoniae and Enterococcus faecalis, antibiotic-resistant gram-negative bacteria, cause serious cases of prolonged UTIs, increasing healthcare costs and potentially even leading to the death of an affected patient. This review discusses current knowledge about the increasing resistance to currently recommended antibiotics for UTI therapy, as well as novel therapeutic options. Traditional antibiotics are still a part of the therapy guidelines for UTIs, although they are often not effective and have serious side effects. Hence, novel drugs are being developed, such as combinations of ß-lactam antibiotics with cephalosporins and carbapenems. Siderophoric cephalosporins, such as cefiderocol, have shown potential in the treatment of individuals with significant gram-negative bacterial infections, as well as aminoglycosides, fluoroquinolones and tetracyclines that are also undergoing clinical trials. The use of cranberry and probiotics is another potential curative and preventive method that has shown antimicrobial and anti-inflammatory effects. However, further studies are needed to assess the efficacy and safety of probiotics containing cranberry extract for UTI prevention and treatment. An emerging novel approach for UTI treatment is the use of immuno-prophylactic vaccines, as well as different nanotechnology solutions such as nanoparticles (NP). NP have the potential to be used as delivery systems for drugs to specific targets. Furthermore, nanotechnology could enable the development of nano antibiotics with improved features by the application of different NPs in their structure, such as gold and copper NPs. However, further high-quality research is required for the synthesis and testing of these novel molecules, such as safety evaluation and pharmacovigilance.

Covid-19 a triggering factor of autoimmune and multi-inflammatory diseases.

SARS-CoV-2 virus has attracted a lot of attention globally due to the autoimmune and inflammatory processes that were observed during the development of Covid-19 disease. Excessive activation of immune response and triggering of autoantibodies synthesis as well as an excessive synthesis of inflammatory cytokines and the onset of cytokine storm has a vital role in the disease outcome and the occurring autoimmune complications. This scenario is reminiscent of infiltration of lymphocytes and monocytes in specific organs and the increased production of autoantibodies and chemoattractants noted in other inflammatory and autoimmune diseases. The main goal of this study is to investigate the complex inflammatory processes that occur in Covid-19 disease and to find similarities with other inflammatory diseases such as multiple sclerosis (MS), acute respiratory distress syndrome (ARDS), rheumatoid arthritis (RA) and Kawasaki syndrome to advance existing diagnostic and therapeutic protocols. The therapy with Interferon-gamma (IFN-γ) and the use of S1P receptor modulators showed promising results. However, there are many unknowns about these mechanisms and possible novel therapies. Therefore, the inflammation and autoimmunity triggered by Covid-19 should be further investigated to improve existing diagnostic procedures and therapeutic protocols for Covid-19.

Cellular therapeutic potential of genetically engineered stem cells in cancer treatment.

Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Epidemiology and Long-Term Outcomes in a Strictly Defined Cohort.

Background: A subset of encapsulated/circumscribed follicular variant of papillary thyroid carcinoma (FVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reduce overtreatment of a low-risk tumor. Study objectives were to describe the epidemiology and long-term outcomes of NIFTP in a high-volume, urban, tertiary referral center. Methods: Among patients enrolled in the Boston Medical Center (BMC) Thyroid Cancer Registry, 110 cases of FVPTC underwent index thyroid surgery at BMC between 2000 and 2016. Historically, BMC pathologists assess all malignant nodules using sections ≤0.3 cm with evaluation of the entire nodule and capsule. After review of pathology reports to identify potential NIFTPs, slides were rereviewed using criteria established by the NIFTP Working Group in 2016 and 2018. We evaluated interobserver reliability using Cohen's Kappa coefficient. Results: Among 110 FVPTCs, 15 (13%) met NIFTP criteria; 11 women and 4 men, age range 31-64 (mean 47.5) years. Mean tumor diameter was 1.7 cm (compared with 2.2 cm for FVPTC). Among NIFTP cases, there were no lymph node metastases, distant metastases, or tumor recurrences. All NIFTP cases were American Thyroid Association (ATA) low risk compared with only 68% of FVPTC (p = 0.011). Among FVPTCs, 14% had positive lymph nodes at index operation. Four patients (4%) had distant metastases. Mean follow-up time was 46 and 69 months for FVPTC and NIFTP, respectively. Among FVPTCs with an excellent response to therapy (2015 ATA guidelines), there were no recurrences. Just over half (n = 8) of patients with NIFTP received postoperative radioactive iodine (RAI) therapy. Concordance between pathologists was high for ruling out NIFTP (75%), but only 36% for ruling in NIFTP. Overall, for NIFTP designation, Cohen's Kappa was 0.39, which is considered fair. Conclusions: Although this is a relatively small cohort, all NIFTP specimens underwent updated pathology review consistent with current guidelines; mean follow-up was nearly 6 years. NIFTP represents a small fraction of the total papillary neoplasia diagnosed at this tertiary referral center (2.3%). None of the NIFTP cohort experienced an adverse oncologic event, and there were no regional or distant metastases. Over 50% of patients with NIFTP received RAI. Thus, the NIFTP reclassification may substantially reduce the number of patients who require adjuvant therapies, such as completion surgery or RAI.

Caprini Risk Model Decreases Venous Thromboembolism Rates in Thoracic Surgery Cancer Patients.

BACKGROUND: Extended postoperative chemoprophylaxis is effective in reducing venous thromboembolism (VTE) among general surgical patients. We hypothesized that implementation of the Caprini risk assessment model (RAM) would reduce VTE rates among patients undergoing lung and esophageal cancer surgery. METHODS: The Caprini RAM, consisting of patient risk stratification and extended postoperative chemoprophylaxis with low molecular weight heparin, was implemented on the thoracic surgery service at Boston Medical Center in July 2014. Patients undergoing lung and esophageal cancer resections were enrolled in the postintervention group beginning in July 2014. Provider and patient adherence to treatment protocol was audited. Venous thromboembolism and adverse bleeding events were monitored for 60 days postoperatively. A preintervention control group including esophagectomy and lung cancer resection patients (January 2005 to June 2013) was used for VTE rate comparison. Exclusion criteria included chronic anticoagulation and presence of filters. RESULTS: There were 302 lung and esophageal cancer resection patients in the preintervention cohort, and 64 thoracic cancer resections in the postintervention group. The overall VTE rates for preintervention and postintervention cohorts were 7.3% (22 of 302) and 3.1% (2 of 64), respectively (p = 0.28). Provider adherence to Caprini RAM score assignment was 100%, whereas patient adherence to treatment was 97.4%. There were no adverse bleeding events. CONCLUSIONS: This study demonstrates a trend toward decreased symptomatic VTE after Caprini RAM implementation, as demonstrated among high-risk cancer patients. The absence of bleeding complications and high provider and patient adherence to VTE RAM support the safety and feasibility of a VTE prevention protocol in thoracic surgery patients.

Prevention of Postoperative Venous Thromboembolism in Thoracic Surgical Patients: Implementation and Evaluation of a Caprini Risk Assessment Protocol.

BACKGROUND: Venous thromboembolism (VTE) can be a devastating postoperative complication, with about one-third of VTEs occurring post-discharge. We previously retrospectively evaluated the Caprini VTE risk assessment model (RAM) in postoperative lung and esophageal cancer patients, demonstrating that "high risk" patients were more likely to have a postoperative VTE. In this study, we sought to implement the RAM protocol in thoracic surgical patients to evaluate adherence, safety, and VTE outcomes. STUDY DESIGN: This prospective cohort study at a large safety net hospital included all surgically treated patients within the thoracic surgery division beginning in July 2014. Per RAM protocol, patients with high risk scores were prescribed a total of 30 days of postoperative daily enoxaparin prophylaxis, and moderate risk patients received a total of 10 postoperative days. Adherence and outcome audits were conducted. RESULTS: A total of 126 patients were included for analysis. Provider adherence to RAM score calculation was 99.2% (125 of 126), with appropriate post-discharge prophylaxis prescribed in 96.0% of cases. Twenty-four patients scored high risk (19.2%), 60 were moderate risk (48.0%), and 41 scored low risk (32.8%). Patient adherence to post-discharge enoxaparin prophylaxis was 97.2%. The overall VTE rate was 2.3%, with no post-discharge VTEs or adverse bleeding events. CONCLUSIONS: Implementation of a VTE risk assessment protocol with extended course prophylaxis in high risk patients is safe and feasible for providers and thoracic surgical patients at a large safety net institution with a diverse patient population. Follow-up studies are needed to assess efficacy of the RAM in this surgical population.