Associations Between Reductions in Depressive Symptoms and Reductions in Pain and Anxiety Symptoms and Substance Use: Emulation of a Randomized Trial.

Introduction: Depressive symptoms are linked with pain, anxiety, and substance use. Research estimating whether a reduction in depressive symptoms is linked to subsequent reductions in pain and anxiety symptoms and substance use is limited. Methods: Using data from the Veterans Aging Cohort Study, a multisite observational study of U.S. veterans, the authors used a target trial emulation framework to compare individuals with elevated depressive symptoms (Patient Health Questionnaire-9 score ≥ 10) who experienced reductions in depressive symptoms (Patient Health Questionnaire-9 score < 10) with those whose symptoms persisted (Patient Health Questionnaire-9 score ≥ 10) at the next follow-up visit (on average, 1 year later). Using inverse probability of treatment weighting, the authors estimated ORs and 95% CIs for associations between depressive symptom reduction status and improvement on the following: anxiety symptoms, pain symptoms, unhealthy alcohol use, and use of tobacco, cannabis, cocaine, and/or illicit opioids. Results: Reductions in depressive symptoms were associated with reductions in pain symptoms (OR=1.43, 95% CI=1.01, 2.02), anxiety symptoms (OR=2.50, 95% CI=1.63, 3.83), and illicit opioid use (OR=2.07, 95% CI=1.13, 3.81). Depressive symptom reductions were not associated with reductions in unhealthy alcohol use (OR=0.85, 95% CI=0.48, 1.52) or use of tobacco (OR=1.49, 95% CI=0.89, 2.48), cannabis (OR=1.07, 95% CI=0.63, 1.83), or cocaine (OR=1.28, 95% CI=0.73, 2.24). Conclusions: Reducing depressive symptoms may potentially reduce pain and anxiety symptoms and illicit opioid use. Future work should determine whether reductions achieved through antidepressant medications, behavioral therapy, or other means have comparable impact.

Advancements in tumor-infiltrating lymphocytes: Historical insights, contemporary milestones, and future directions in oncology therapy.

Tumor-infiltrating lymphocytes (TILs) are a subtype of immune cells that infiltrate and accumulate within tumors. Studies proved that TILs can be used as prognostic and predictive markers for cancer patients' responses to immunotherapy. This review explores the modern knowledge of TILs, the challenges and opportunities for utilizing TILs in cancer treatment, such as the rise of therapies under TIL circumstances, the identification of biomarkers for TIL activity, and methods used to isolate and expand TILs for therapeutic use. Ongoing clinical trials and promising results in different cancer types are highlighted, including melanoma, ovarian, and colorectal cancer. This also focuses on ongoing efforts to improve TIL-based therapies by identifying the specific subsets of TILs that are most effective in treating cancer and developing methods to increase the functionality and persistence of TILs in the tumor microenvironment. The article recapitulates the present state TILs therapy, ongoing research, and improvements to its potency.

Does smoking cessation reduce other substance use, psychiatric symptoms, and pain symptoms? Results from an emulated hypothetical randomized trial of US veterans.

BACKGROUND: Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. METHODS: We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. RESULTS: Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. CONCLUSIONS: While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

Management of Breast Intraductal Papilloma Diagnosed on Core Needle Biopsy: Excision or Follow-up?

Introduction Management of intraductal papillomas (IDPs) diagnosed on core needle biopsy (CNB) remains controversial. We report our experience of IDPs identified on CNB, our institutional rates of upgradation to atypia/malignancy as well as radiologic/pathologic features that may allow selection for surgery as well as those for safe observation. Methods The study is a retrospective review of patient records from 2012 to 2019, at a tertiary care hospital in Pakistan. Data was analyzed using Statistical Package for Social Sciences (SPSS), version 21.0 (IBM Corp., Armonk, NY). Associations between various patient factors were assessed using Pearson's chi-square test. Results This study included a total of 55 female patients with IDPs, with a mean age of 54.67 ± 15.57 years. On CNB, 69.1% (n = 38) of patients had IDP without atypia while 30.9% (n = 17) had IDP with atypia, with single IDPs being the most common lesions on excisional biopsy. Overall, of all CNB-diagnosed IDPs, only 4/55 (7.3%) demonstrated upgradation (3/4 to DCIS, 1/4 showed atypia) on excisional biopsy, and all these upgraded cases had failed to demonstrate atypia on initial CNB. Conclusion CNB-identified cases of IDPs are rarely upgraded on excision and thus routine excision in all cases may be unnecessary. Appropriate patient selection based on radiology-pathology findings should be done. Those with suspicious findings on imaging as well as those that demonstrate atypia on CNB must be excised.

Risk of Potential Invasive Non-Tuberculous Mycobacterial Infection in Major Cardiothoracic Surgeries.

Nontuberculous Mycobacteria (NTM) commonly colonise municipal water supplies and cause healthcare-associated outbreaks. Although the infections are rare, they are associated with high mortality.  Aerosolization of NTM from colonised Heater cooler devices causes invasive infections in cardiac surgery patients. These units are widely used in open-chest heart surgery as an essential part of extracorporeal circulation but have been suggested as being a risk for infection.  Water disinfection as well as effective engineering-related mitigation strategies should be designed to decrease the burden of NTM in the hospital water supply. Key Words: Nontuberculous Mycobacteria, Heater cooler devices, Endocarditis, Water, Cardiothoracic surgeries.

Differing radiation exposure in scrub technicians and rotating staff in Cardiac catheterization laboratory: occupation matters.

BACKGROUND: Radiation exposure is a significant hazard associated with invasive Cardiology, with most studies based on primary operator exposure. This prospective, observational study aimed to find out over lead radiation exposure as effective dose acquired by non-physician staff comprising scrub technicians and rotating staff in the cath laboratory. Effective dose (ED) measured per procedure via Raysafe i2®dosimeter badges worn by both rotating staff and scrub technicians over lead aprons along with dose area product (DAP), fluoroscopy time (FT) and procedure time (PT) in minutes was collected prospectively over forty-six invasive Cardiology procedures. RESULTS: This study shows that rotating staff acquire higher ED in comparison with their scrub technician colleagues in diagnostic, interventional and electrophysiology cases. However, a statistically significant difference in radiation exposure of both staff groups was demonstrated in diagnostic and interventional Cardiology procedures, with p values of 0.04 and 0.01, respectively. CONCLUSIONS: These findings highlight occupational role and mobility around fluoroscopic sources as major factors in radiation exposure, which should be addressed within current radiation protection practices.

Characterization of patients with brain metastases referred to palliative care.

PURPOSE: In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center. METHODS: Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes. RESULTS: While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM. CONCLUSIONS: Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.

Impact of Decarceration Plus Alcohol, Substance Use, and Mental Health Screening on Life Expectancies of Black Sexual Minority Men and Black Transgender Women Living With HIV in the United States: A Simulation Study Based on HPTN 061.

BACKGROUND: Given the disproportionate rates of incarceration and lower life expectancy (LE) among Black sexual minority men (BSMM) and Black transgender women (BTW) with HIV, we modeled the impact of decarceration and screening for psychiatric conditions and substance use on LE of US BSMM/BTW with HIV. METHODS: We augmented a microsimulation model previously validated to predict LE and leading causes of death in the US with estimates from the HPTN 061 cohort and the Veteran's Aging Cohort Studies. We estimated independent associations among psychiatric and substance use disorders, to simulate the influence of treatment of one condition on improvement on others. We used this augmented simulation to estimate LE for BSMM/BTW with HIV with a history of incarceration under alternative policies of decarceration (ie, reducing the fraction exposed to incarceration), screening for psychiatric conditions and substance use, or both. RESULTS: Baseline LE was 61.3 years. Reducing incarceration by 25%, 33%, 50%, and 100% increased LE by 0.29, 0.31, 0.53, and 1.08 years, respectively, versus no reductions in incarceration. When reducing incarceration by 33% and implementing screening for alcohol, tobacco, substance use, and depression, in which a positive screen triggers diagnostic assessment for all psychiatric and substance use conditions and linkage to treatment, LE increased by 1.52 years compared with no screening or decarceration. DISCUSSION: LE among BSMM/BTW with HIV is short compared with other people with HIV. Reducing incarceration and improving screening and treatment of psychiatric conditions and substance use could substantially increase LE in this population.

The cross-talk between macrophages and tumor cells as a target for cancer treatment.

Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associated macrophages (TAMs) protect and support the growth, proliferation, and invasion of tumor cells and promote suppression of antitumor immunity. TAM abundance is closely associated with poor outcome of cancer, with impediment of chemotherapy effectiveness and ultimately a dismal therapy response and inferior overall survival. Thus, cross-talk between cancer cells and TAMs is an important target for immune checkpoint therapies and metabolic interventions, spurring interest in it as a therapeutic vulnerability for both hematological cancers and solid tumors. Furthermore, targeting of this cross-talk has emerged as a promising strategy for cancer treatment with the antibody against CD47 protein, a critical macrophage checkpoint recognized as the "don't eat me" signal, as well as other metabolism-focused strategies. Therapies targeting CD47 constitute an important milestone in the advancement of anticancer research and have had promising effects on not only phagocytosis activation but also innate and adaptive immune system activation, effectively counteracting tumor cells' evasion of therapy as shown in the context of myeloid cancers. Targeting of CD47 signaling is only one of several possibilities to reverse the immunosuppressive and tumor-protective tumor environment with the aim of enhancing the antitumor response. Several preclinical studies identified signaling pathways that regulate the recruitment, polarization, or metabolism of TAMs. In this review, we summarize the current understanding of the role of macrophages in cancer progression and the mechanisms by which they communicate with tumor cells. Additionally, we dissect various therapeutic strategies developed to target macrophage-tumor cell cross-talk, including modulation of macrophage polarization, blockade of signaling pathways, and disruption of physical interactions between leukemia cells and macrophages. Finally, we highlight the challenges associated with tumor hypoxia and acidosis as barriers to effective cancer therapy and discuss opportunities for future research in this field.

Cytogenetic profile of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan.

Objective: To determine the frequencies of different cytogenetic abnormalities in patients of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan. Methods: It was descriptive cross-sectional study conducted in Hematology Department of a Tertiary care referral institute from June 2015 to July 2017. All newly diagnosed cases of Acute Leukemia were analyzed. Cytogenetic analysis was performed on bone marrow aspirate samples using Giemsa-trypsin banding technique. Karyotypes were identified and interpreted according to ISCN criteria. Results: A total of 355 newly diagnosed patients of Acute Leukemia were analyzed. Out of these, 180 patients had AML and 175 had ALL. In Acute Myeloid Leukemia chromosomal abnormalities were detected in 28.2 % cases. Of these the common ones included t(8;21),t(15;17),+8, Inversion 16 and Monosomy 7. Other abnormalities included Complex karyotype, Down's syndrome related AML, Hyperdiploidy, del 16q,-8,+Y and t(3p;17q)del 10. In Acute Lymphoblastic Leukemia chromosomal abnormalities were detected in 40% cases. Common ones included Hyperdiploidy, Tetraploidy and t(9;22). Other abnormalities included t(1;19) and t(2;8)t(8;14). Conclusion: Cytogenetically favorable abnormalities are commonest occurring chromosomal defects in both Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan, i.e., t(8;21) in AML and Hyperdiploidy in ALL.

EquiPrEP: An implementation science protocol for promoting equitable access and uptake of long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP).

BACKGROUND: Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) was approved by the U.S. Food and Drug Administration in December 2021. This initial phase of implementation represents a prime opportunity to ensure equitable LAI-PrEP provision to communities often underrepresented in PrEP care before disparities in access and uptake emerge. Herein, we describe the EquiPrEP Project which utilizes an equity-oriented implementation science framework to optimize LAI-PrEP rollout in an urban safety-net clinic in New York City. METHODS: The primary objectives of this project are to: (1) increase LAI-PrEP initiation overall; (2) increase uptake among groups disproportionately impacted by the HIV epidemic; (3) preserve high PrEP retention while expanding use; and (4) identify barriers and facilitators to LAI-PrEP use. EquiPrEP will enroll 210 PrEP-eligible participants into LAI-PrEP care with planned follow-up for one year. We will recruit from the following priority populations: Black and/or Latine men who have sex with men, Black and/or Latine cisgender women, and transgender women and nonbinary individuals. To evaluate implementation of LAI-PrEP, we will utilize equity-focused iterations of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR), in addition to longitudinal surveys and qualitative interviews. DISCUSSION: Novel LAI-PrEP formulations carry tremendous potential to revolutionize the field of HIV prevention. Implementation strategies rooted in equity are needed to ensure that marginalized populations have access to LAI-PrEP and to address the structural factors that hinder initiation and retention in care.

Associations between police harassment and distrust in and reduced access to healthcare among Black sexual minority men: A longitudinal analysis of HPTN 061.

OBJECTIVE: Evaluate associations between racialized and homophobia-based police harassment (RHBPH) and healthcare distrust and utilization among Black Sexual Minority Men (BSMM). METHODS: We utilized data from a longitudinal cohort study from HIV Prevention Trials Network (HPTN) 061 with baseline, six and 12 month follow-up assessments. Using multivariable analysis, we evaluated associations between RHBPH and healthcare distrust and utilization reported at the 6 and 12 month visits. RESULTS: Of 1553 BSMM present at baseline, 1160 were available at six-month follow-up. In multivariable analysis, increasing frequency of RHBPH was associated with increasing levels of distrust in healthcare providers (aOR 1.31, 95% CI: 1.00, 1.74) and missing 50% or more of healthcare visits at six-month follow-up (aOR 1.93, 95% CI: 1.09, 3.43). CONCLUSIONS: Recent experiences of RHBPH are associated with reduced trust in and access to healthcare among BSMM, with more frequent RHBPH associated with greater vulnerability.

Risk Factors for Stroke in the Young (18-45 Years): A Case-Control Analysis of INTERSTROKE Data from 32 Countries.

BACKGROUND: It is not clear whether conventional vascular risk factors are responsible for most strokes in patients younger than 45 years of age. Our objective was to evaluate the association of common risk factors with stroke in individuals under 45 years. METHODS: INTERSTROKE was a case-control study carried out in 32 countries between 2007 and 2015. Patients presenting within 5 days of symptom onset of a first stroke were enrolled as cases. Controls were age and sex matched to cases and had no history of stroke. Cases and controls underwent similar evaluations. Odds ratios (ORs) and population attributable risks (PARs) were calculated to determine the association of various risk factors with all stroke, ischemic stroke, and intracranial hemorrhage, for patients 45 years of age or younger. FINDINGS: 1,582 case-control pairs were included in this analysis. The mean age of this cohort was 38.5 years (SD 6.32). Overall, 71% strokes were ischemic. Cardiac causes {OR: 8.42 (95% confidence interval [CI]: 3.01-23.5)}; binge drinking of alcohol (OR: 5.44 [95% CI: 1.81-16.4]); hypertension (OR: 5.41 [95% CI: 3.40-8.58]); ApoB/ApoA1 ratio (OR: 2.74 [95% CI: 1.69-4.46]); psychosocial stress (OR: 2.33 [95% CI: 1.01-5.41]); smoking (OR: 1.85 [95% CI: 1.17-2.94]); and increased waist-to-hip ratio (OR: 1.69 [95% CI: 1.04-2.75]) were the most important risk factors for ischemic stroke in these young cases. For intracerebral hemorrhage, only hypertension (OR: 9.08 [95% CI: 5.46-15.1]) and binge drinking (OR: 4.06 [95% CI: 1.27-13.0]) were significant risk factors. The strength of association and population attributable risk (PAR) for hypertension increased with age (PAR 23.3% in those <35 years of age, 50.7% in 35-45 years of age). INTERPRETATION: Conventional risk factors such as hypertension, smoking, binge drinking of alcohol, central obesity, cardiac causes, dyslipidemia, and psychosocial stress are important risk factors for stroke in those younger than 45 years of age. Hypertension is the most significant risk factor in all age groups and across all regions and both stroke subtypes. These risk factors should be identified and modified in early adulthood to prevent strokes in young individuals.

Identification of Non-steroidal Aromatase Inhibitors via In silico and In vitro Studies

INTRODUCTION: Breast cancer is the most common cancer affecting women worldwide, including Pakistan. More than half of breast cancer patients have hormone-dependent breast cancer, which is developed due to the over-production of estrogen (the main hormone in breast cancer). METHOD: The biosynthesis of estrogen is catalyzed by the aromatase enzyme, which thus serves as a target for the treatment of breast cancer. During the current study, biochemical, computational, and STD-NMR methods were employed to identify new aromatase inhibitors. A series of phenyl-3- butene-2-one derivatives 1-9 were synthesized and evaluated for human placental aromatase inhibitory activity. Among them, four compounds 2, 3, 4, and 8 showed a moderate to weak inhibitory activity (IC50 = 22.6 - 47.9 µM), as compared to standard aromatase inhibitory drugs, letrozole (IC50 = 0.0147 ± 1.45 µM), anastrozole (IC50 = 0.0094 ± 0.91 µM), and exemestane (IC50 = 0.2 ± 0.032 µM). Kinetic studies on two moderate inhibitors, 4 and 8, revealed a competitive- and mixed-type of inhibition, respectively. RESULT: Docking studies on all active compounds indicated their binding adjacent to the heme group and interaction with Met374, a critical residue of aromatase. STD-NMR further highlighted the interactions of these ligands with the aromatase enzyme. CONCLUSION: STD-NMR-based epitope mapping indicated close proximity of the alkyl chain followed by an aromatic ring with the receptor (aromatase). These compounds were also found to be non-cytotoxic against human fibroblast cells (BJ cells). Thus, the current study has identified new aromatase inhibitors (compounds 4, and 8) for further pre-clinical and clinical research.

Postoperative Fillers Reduce Revision Rates in Rhinoplasty.

Background: Rhinoplasty is a complex procedure with revision rates of up to 17%. Even minor imperfections after surgery can be significant. Objectives: This review aims to investigate the use of hyaluronic acid (HA) fillers postaesthetic rhinoplasty and assess the rhinoplasty practice of the senior author. Methods: From the senior author's practice, case records were obtained for patients who underwent surgery followed by nonsurgical rhinoplasty between 2015 and 2022. Data were retrospectively obtained and analyzed. The variables measured included the number of patients treated with fillers postoperatively, volume and type of filler used, locations of injection, and frequency of injections and complications. Results: Eight hundred patients underwent rhinoplasty between March 2015 and March 2022, and 10.6% (n = 85) of these underwent nonsurgical rhinoplasty using the HA filler for postoperative imperfections. The Juvederm 2 filler (Allergan, Irvine, CA) was mainly used with a mean volume of 0.2 mL. A total of 11.8% (n = 10) of patients had fillers for a second time and 3.5% (n = 3) required a third filler. The majority of patients had fillers in the rhinon area (82.3%; n = 70), and no complications were reported, with patient satisfaction levels being good. Conclusions: Often, there is hesitancy to use fillers after surgery due to the assumption that fillers will be required in the long term and complication rates can be high for postrhinoplasty nose fillers. From our series, we conclude that after surgery, fillers last for a greater time period than those used purely for primary augmentation. Hence, the authors recommend rhinoplasty surgeons to consider HA filler use for patients troubled by postsurgery surface irregularities.

Potential health benefits of integrated screening strategies for alcohol, tobacco, other substance use, depression, anxiety, and chronic pain among people living with HIV in the USA: a mathematical modelling study.

BACKGROUND: Alcohol use, tobacco use, and other substance use often co-occur with depression, anxiety, and chronic pain, forming a constellation of alcohol, substance, and mood-related (CASM) conditions that disproportionately affects people with HIV in the USA. We used a microsimulation model to evaluate how alternative screening strategies accounting for CASM interdependence could affect life expectancy in people with HIV in the USA. METHODS: We augmented a microsimulation model previously validated to predict US adult life expectancy, including in people with HIV. Using data from the Veterans Aging Cohort Study, we incorporated CASM co-occurrence, inferred causal relationships between CASM conditions, and assessed the effects of CASM on HIV treatment and preventive care. We simulated an in-care HIV cohort exposed to alternative CASM screening and diagnostic assessment strategies, ranging from currently recommended screenings (alcohol, tobacco, and depression, with diagnostic assessments for conditions screening positive) to a series of integrated strategies (screening for alcohol, tobacco, or depression with additional diagnostic assessments if any screened positive) to a maximal saturation strategy (diagnostic assessments for all CASM conditions). FINDINGS: The saturation strategy increased life expectancy by 0·95 years (95% CI 0·93-0·98) compared with no screening. Recommended screenings provided much less benefit: 0·06 years (0·03-0·09) gained from alcohol screening, 0·08 years (0·06-0·11) from tobacco screening, 0·10 years (0·08-0·11) from depression screening, and 0·25 years (0·22-0·27) from all three screenings together. One integrated strategy (screening alcohol, tobacco, and depression with diagnostic assessment for all CASM conditions if any screened positive) produced near-maximal benefit (0·82 years [0·80-0·84]) without adding substantial screening burden, albeit requiring additional diagnostic assessments. INTERPRETATION: Primary care providers for people with HIV should consider comprehensive diagnostic assessment of CASM conditions if one or more conditions screen positive. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Multidimensional Quality of Life After Robotic Versus Laparoscopic Surgery for Rectal Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Maximizing patients' quality of life (QoL) is a central goal in surgical oncology. Currently, both laparoscopic and robotic surgery are viable options in rectal cancer (RC) resections. The aim of this systematic review was to analyze the differences in postoperative QoL between the two operative modalities. METHODOLOGY: This review was conducted in adherence to the PRISMA guidelines. MEDLINE, Embase, Scopus, and CENTRAL databases were searched for articles comparing QoL in patients undergoing laparoscopic versus robotic surgery for RC. Seven studies were included (two randomized controlled trials, four prospective cohorts, and one retrospective cohort) out of which six reported data suitable for meta-analysis. Global QoL and QoL subdomains, such as physical and social functioning, were meta-analyzed using a random-effects model. Risk of bias was assessed using the ROBINS-I and Cochrane RoB-2 tools. RESULTS: Data on 869 patients (440 laparoscopic and 429 robotic surgery) across six studies were meta-analyzed. There was no significant difference in global QoL (Mean Difference:-0.43 [95% Confidence Interval:-3.49-2.62]). Physical functioning was superior after robotic surgery (1.92 [0.97-2.87]). However, nausea/vomiting, pain, and fatigue did not differ between groups. Perception of body image was worse after laparoscopic surgery (-5.06 [-9.05- -1.07]). Other psychosocial subdomains (emotional, cognitive, role, and social functioning) were comparable between groups. CONCLUSION: Laparoscopic and robotic surgery for RC have comparable QoL overall, for both physical and psychological dimensions. Our results may assist the management-related decision-making in surgical treatment of RC.

Cessation of self-reported opioid use and impacts on co-occurring health conditions.

BACKGROUND: Among veterans in care reporting opioid use, we investigated the association between ceasing opioid use on subsequent reduction in report of other substance use and improvements in pain, anxiety, and depression. METHODS: Using Veterans Aging Cohort Study survey data collected between 2003 and 2012, we emulated a hypothetical randomized trial (target trial) of ceasing self-reported use of prescription opioids and/or heroin, and outcomes including unhealthy alcohol use, smoking, cannabis use, cocaine use, pain, and anxiety and depressive symptoms. Among those with baseline opioid use, we compared participants who stopped reporting opioid use at the first follow-up (approximately 1 year after baseline) with those who did not. We fit logistic regression models to estimate associations with change in each outcome at the second follow-up (approximately 2 years after baseline) among participants with that condition at baseline. We examined two sets of adjusted models that varied temporality assumptions. RESULTS: Among 2473 participants reporting opioid use, 872 did not report use, 606 reported use, and 995 were missing data on use at the first follow-up. Ceasing opioid use was associated with no longer reporting cannabis (adjusted odds ratio [AOR]=1.82, 95% confidence interval [CI] 1.10, 3.03) and cocaine use (AOR=1.93, 95% CI 1.16, 3.20), and improvements in pain (AOR=1.53, 95% CI 1.05, 2.24) and anxiety (AOR=1.56, 95% CI 1.01, 2.41) symptoms. CONCLUSION: Cessation of opioid misuse may be associated with subsequent cessation of other substances and reduction in pain and anxiety symptoms, which supports efforts to screen and provide evidence-based intervention where appropriate.

Aneurysm Geometry Analyzed by the Novel Three-Dimensional Tomographic Ultrasound Relates to Abdominal Aortic Aneurysm Growth.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are increasingly screen-detected and many small aneurysms enter surveillance. Computed tomography identifies characteristics that can predict subsequent AAA growth but ionizing radiation and nephrotoxic contrast disadvantage its use in surveillance. We investigated whether duplex and 3-dimensional tomographic ultrasound identified features associated with AAA growth in patients on AAA surveillance. METHODS: Duplex and three-dimensional tomographic ultrasound imaging was performed independently by 2 vascular scientists in 128 AAA surveillance patients who all had AAA growth measured over at least 2 years. Diameter, cross-sectional area, length, volume, wall thickness/volume, and intraluminal thrombus were measured. Pulsatility using maximum systolic and minimum diastolic diameters corrected for diameter and distensibility (consisting of strain and stiffness) were also calculated. RESULTS: AAA growth rate correlated with AAA diameter (r 0.43), volume (r 0.46), and cross-sectional area (r 0.42) (P < 0.01). Measuring wall thickness was inaccurate, but wall volume (corrected for AAA volume) inversely related to growth rate (r -0.43, P < 0.01). On a multivariate analysis, diameter and wall volume (r2adjusted 0.22, P < 0.01) improved prediction of growth rate compared with diameter alone (r2adjusted 0.18, P < 0.01). Intraluminal thrombus volume, strain distensibility, and elastic distensibility were not significantly associated with AAA growth. CONCLUSIONS: AAA growth most strongly related to AAA volume and inversely to wall volume. AAA volume and wall volume may prove useful in the prediction of AAA growth rates.

Reduced tumor growth in EP2 knockout mice is related to signaling pathways favoring an increased local anti­tumor immunity in the tumor stroma.

Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well­established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor­stroma, at conditions of reduced disease progression due to decreased host inflammation. In the present study, wild­type tumor cells, producing high levels of prostaglandin E2 (MCG 101 cells, EP2+/+), were inoculated into EP2 knockout (EP2­/­) and EP2 wild­type (EP2+/+) mice. Solid tumors were dissected into tumor­ and tumor­stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. Immunohistochemistry was used to confirm adequate dissections of tissue compartments, and to assess cell proliferation (Ki­67), prostaglandin enzymes (cyclooxygenase 2) and immunity biomarkers (CD4 and CD8) at the protein level. Microarray analyses revealed statistically significant alterations in gene expression in the tumor­stroma compartment, while significantly less pathway alterations occurred in the tumor tissue compartment. The host knockout of EP2 receptors led to a significant downregulation of cell cycle regulatory factors in the tumor­stroma compartment, while interferon γ­related pathways, chemokine signaling pathways and anti­tumor chemokines [chemokine (C­X­C motif) ligand 9 and 10] were upregulated in the tumor compartment. Thus, such gene alterations were likely related to reduced tumor growth in EP2­deficient hosts. On the whole, pathway analyses of both tumor­ and tumor­stroma compartments suggested that absence of host EP2 receptor signaling reduces 'remodeling' of tumor microenvironments and increase local immunity, probably by decreased productions of stimulating growth factors, perhaps similar to well­recognized physiological observations in wound healing.