Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells.

Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1-7. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy7-9; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and functionally distinct resistant types. These resistant types are largely predetermined by molecular differences between cells before drug addition and not by extrinsic factors. Changes in the dose and type of drug can switch the resistant type of an initial cell, resulting in the generation and elimination of certain resistant types. Samples from patients show evidence for the existence of these resistant types in a clinical context. We observed diversity in resistant types across several single-cell-derived cancer cell lines and cell types treated with a variety of drugs. The diversity of resistant types as a result of the variability in intrinsic cell states may be a generic feature of responses to external cues.

Clinical and laboratory profile of Expanded Dengue Syndrome: experience of 2019 outbreak from Dhaka, Bangladesh.

BACKGROUND OBJECTIVES: Bangladesh is afflicted with periodic dengue outbreak every few years and one of the worst upsurges was recorded in 2019 during which there was an increasing trend of dengue with unusual symptoms which were not so common before. This study aims to describe the experience of three tertiary care centres of Dhaka regarding the clinical and laboratory, hospital outcome and management profile of the Expanded Dengue Syndrome (EDS) cases admitted from the 2019 outbreak. METHODS: The current work was a cross-sectional observational study which took place from August 1 to December 31 2019 at three major tertiary care centres in Dhaka, Bangladesh. Out of total 2017 screened dengue cases, 49 met the inclusion criteria and 39 were enrolled after taking informed written consent. Data was analysed using Microsoft Excel and Graph pad prism 9.3.1. A probability value of p<0.05 was considered statistically significant. RESULTS: Out of the 39 cases, majority were male (79.49%) with median (±IQR) age of 33(±9) years. Hypertension (4; 10.26%) was the most commonly associated co-morbidity. Among the systemic manifestations, most prevalent was hepatitis (38.49%) followed by encephalopathy (12.82%). Majority of the patients were suffering from primary infection (85%). Case fatality rate was 15.38%. Hepatitis and meningoencephalitis were the predominant cause of death. This study records the only known case report of Acute respiratory dress syndrome (ARDS) complicating dengue from Bangladesh. None of the patients from our cohort were managed by steroids. Only two (5.13%) out of 39 cases received antibiotics. INTERPRETATION CONCLUSION: In the year 2019, an unusual rise in EDS cases with about 15.4% fatalities were observed in this study. Hepatitis was the most common presentation and cause of death. Here, we report the first ARDS case encountered in Bangladesh. Despite the multifaceted presentation of EDS, indiscriminate use of antibiotics and steroid was minimal. Early recognition of multifarious features of EDS is important for choosing the targeted treatment option which can avert many deaths. The results of this study underline the necessity for more in-depth research into the risk factors that are contributing to mortality in EDS cases.

The Virtual Face of Colon and Rectal Surgery Training in the USA: An In-Depth Evaluation and Analysis of Fellowship Programs Website Content.

BACKGROUND: With an ever-evolving digital and virtual world hastened by the COVID-19 pandemic, prospective colon and rectal surgery fellowship applicants must rely on online sources of information, such as websites, rather than in-person visits to fellowship programs. This study analyzes and evaluates the content and accuracy of colon and rectal surgery fellowship program websites. METHODS: The Fellowship and Residency Electronic and Interactive Database website provides a complete collection of colon and rectal surgery fellowship websites based in the USA. The accessibility of the websites was verified via Google search, and relevant content for the applicants was evaluated based on 50-point criteria. RESULTS: Analysis of 60 fellowship program websites was conducted, out of which only a fifth (20%) were kept up to date. Twenty-seven (45%) websites fulfilled 50% of the 50-point criteria. The most and least included data points were program overview (69%) and residential/housing information (24%). Most websites contained basic information relevant to international applicants but lacked crucial information such as visa sponsorship (12%) and city information (23%). CONCLUSION: An informative and easily accessible website is essential for prospective applicants to choose the best program for their career goals and academic needs. This study highlighted multiple areas for potential improvement in the colon and rectal surgery program websites. Individual colon and rectal surgery programs may benefit and attract more candidates to their programs through a fully optimized website design and content.

Evaluation of the Antimicrobial Activity of Phytochemicals from Tea and Agarwood Leaf Extracts against Isolated Bacteria from Poultry and Curd.

Antibiotic-resistant bacteria are becoming increasingly common, leading to a global health crisis. The effects of abusing antibiotics not only increase pathogenic resistance but also cause various diseases and syndromes. Gut microbiota contains many beneficial roles for health, while antibiotics kill both pathogens and gut microbiota which is considered one of the major side effects of antibiotics. In fact, new antibiotic compounds are needed in this urgent scenario; phytoremediation is the oldest but most effective method, and research on the antibacterial properties of several types of medicinal plants has already been conducted. Tea and agarwood plants are well known for their economic contribution in both beverage and cosmetic production, as well as for their medicinal value. In this study, tea and agarwood leaf extracts were analyzed for their antimicrobial activity against both pathogenic and beneficial bacteria. Fresh tea (Camellia sinensis) leaves were collected in three varieties, namely, BT-6 from Sylhet, BT-7 from Moulvibazar, and BT-8 from Habiganj; also, green tea (nonfermented tea), black tea (fully fermented tea), and agarwood (Aquilaria malaccensis) were collected from Sylhet region of Bangladesh. Unlike commercial antibiotics, which have side effects on probiotics (beneficiary bacteria), leaf extract activities were analyzed to check if they had positive effects on probiotics that can be found in the gastrointestinal tract as well as dairy products. Potential beneficiary bacteria, Lysinibacillus macroides strain SRU-001 (NCBI accession no. MW665108), and pathogenic bacteria, Aeromonas caviae strain YPLS-62 (NCBI accession no. MW666783), were isolated from the small intestine of poultry and curd, respectively. Tea and agarwood leaves (5 g powder/80 mL methanol) with solvents were kept for seven days at room temperature, and extracts were applied for antimicrobial assays by the disc diffusion assay against the isolated bacteria. 50 µL of each leaf extract was examined against 50 µL of each bacterial culture, where gentamicin was a control. After 24 hours of incubation, tea and agarwood leaf extracts showed an 11-15 mm zone of inhibition against pathogenic A. caviae, while only BT-8 showed 7 mm (disc diameter 6 mm) against probiotic L. macroides. However, compared to leaf extracts, gentamicin showed a 27 mm zone of inhibition against both L. macroides strain SRU-001 and A. caviae strain YPLS-62 bacteria. This research clearly indicates that gentamicin kills both pathogenic and beneficiary bacteria, while leaf extracts from tea and agarwood plants contain antimicrobial activity against only pathogenic A. caviae but no effects on probiotic L. macroides. This outcome indicates not only the potential therapeutic values of tea and agarwood leaves as antibiotics over commercial antibiotics but also the chance of having pathogens in curd and potential beneficial bacteria from the poultry small intestine.

Robotics and artificial intelligence in healthcare during COVID-19 pandemic: A systematic review.

The outbreak of the COVID-19 pandemic is unarguably the biggest catastrophe of the 21st century, probably the most significant global crisis after the second world war. The rapid spreading capability of the virus has compelled the world population to maintain strict preventive measures. The outrage of the virus has rampaged through the healthcare sector tremendously. This pandemic created a huge demand for necessary healthcare equipment, medicines along with the requirement for advanced robotics and artificial intelligence-based applications. The intelligent robot systems have great potential to render service in diagnosis, risk assessment, monitoring, telehealthcare, disinfection, and several other operations during this pandemic which has helped reduce the workload of the frontline workers remarkably. The long-awaited vaccine discovery of this deadly virus has also been greatly accelerated with AI-empowered tools. In addition to that, many robotics and Robotics Process Automation platforms have substantially facilitated the distribution of the vaccine in many arrangements pertaining to it. These forefront technologies have also aided in giving comfort to the people dealing with less addressed mental health complicacies. This paper investigates the use of robotics and artificial intelligence-based technologies and their applications in healthcare to fight against the COVID-19 pandemic. A systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method is conducted to accumulate such literature, and an extensive review on 147 selected records is performed.

Comparison of neck length, relative neck length and height with incidence of cervical spondylosis.

OBJECTIVE: To compare the neck length, relative neck length and height between patients with cervical spondylosis and healthy subjects. METHODS: This case control study was conducted at Patel hospital, Karachi after the ethical approval of Bahria University Medical and Dental College (BUMDC) and Patel hospital from September 2018 - February 2019. It enrolled eighty eight cases of cervical spondylosis and eighty eight healthy subjects. Radiographs were taken in the lateral view and neck length was measured as the distance from external occipital protuberance to seventh cervical vertebra spinous process. Then relative neck length was measured by dividing the neck length with height and multiplying it by 100. The Kellgren Lawrence grade scale was used to assess the severity of cervical spondylosis. RESULTS: A total of 176 participants were analyzed. It was found that the height remains the significant determinant. The comparison of cases with control group was done using independent T-test which showed that the cases were significantly shorter than controls with a p-value < 0.05. The other variables such as neck length, and relative neck length were insignificant. CONCLUSION: Short height can be considered as a risk factor for cervical spondylosis. Short-statured individuals should be counseled to adopt measures for the prevention of cervical spondylosis.

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene.

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.

Contributors to post-operative venous thromboembolism risk after breast cancer surgery: A systematic review and meta-analysis.

INTRODUCTION: Venous thromboembolism (VTE) events are a preventable complication for patients undergoing surgery for breast cancer. However, there is a lack of consistency in the existing literature regarding the potential risk factors affecting these individuals. METHODS: This study aimed to investigate the potential risk factors associated with an increased risk of VTE following surgery for breast cancer. Data on patient characteristics such as age, body mass index (BMI), existing comorbidities, smoking history, surgical interventions, duration of hospitalization, and post-operative complications were recorded and analyzed. RESULTS: Thirty-one studies investigating the incidence of VTE following surgical interventions for breast cancer were included. This study included 22,155 female patients with a mean age of 50.8 ± 2.9 years. The weighted mean length of surgery and hospital stay were 382.1 ± 170.0 min and 4.5 ± 2.7 days, respectively. The patients were followed-up for a weighted mean duration of 13.8 ± 21.2 months. The total incidence of VTE events was 2.2% (n = 489). Meta-analysis showed that patients with post-operative VTE had a significantly higher mean age and BMI, as well as longer mean length of surgery (P < 0.05). Comparing the techniques of autologous breast reconstruction showed that the risk of post-operative VTE is significantly higher with deep inferior epigastric perforator (DIEP) flaps, compared with the transverse rectus abdominus myocutaneous and latissimus dorsi myocutaneous flaps (P < 0.05). Compared with delayed reconstruction, immediate reconstruction was associated with a significantly higher incidence of VTE (P < 0.05). Smoking history, length of hospital stay, and Caprini score did not correlate with increased incidence of post-operative VTE. CONCLUSION: The incidence rate of VTE events in patients receiving surgical treatment for breast cancer is 2.2%. Risk factors for developing post-operative VTE in this patient population were found to be older age, increased BMI, extended length of surgical procedures, and DIEP flap reconstruction.

pH-Tolerant Wet Adhesion of Catechol Analogs.

The need for improved wet adhesives has driven research on mussel-inspired materials incorporating dihydroxyphenylalanine (DOPA) and related analogs of the parent catechol, but their susceptibility to oxidation limits practical application of these functionalities. Here, we investigate the molecular-level adhesion of the catechol analogs dihydroxybenzamide (DHB) and hydroxypyridinone (HOPO) as a function of pH. We find that the molecular structure of the catechol analogs influences their susceptibility to oxidation in alkaline conditions, with HOPO emerging as a particularly promising candidate for pH-tolerant adhesives for diverse environmental conditions.

Efficacy and safety of bedaquiline and delamanid in the treatment of drug-resistant tuberculosis in adults: A systematic review and meta-analysis.

Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st, 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval.

Perioperative sildenafil therapy in pulmonary hypertension associated with congenital cardiac disease: An updated meta-analysis.

To provide an updated meta-analysis to evaluate the efficacy and safety of sildenafil on pediatric patients with pulmonary hypertension (PH) associated with congenital heart disease (CHD). To assess the efficacy and safety of sildenafil, five outcomes, time duration of post-operative need for mechanical ventilation, time duration of post-operative ICU stay, length of hospitalization (LOH), the incidence of mortalities and pulmonary arterial pressure to aortic pressure ratio (PAP/AoP) were regarded as primary efficacy outcomes. Standardized mean difference (SMD) was calculated for continuous data. In comparison to the control group (CG), there was a significant decrease in the time duration of ICU stay in the sildenafil group (SG) (SMD = -0.61 [95% CI -1.17, 0.04]; P < 0.01, I2 = 85%). Length of hospitalization was assessed in the sildenafil and control groups (SMD = -0.18 [95% CI -0.67, 0.31] P = 0.05, I2 = 62%). However, there was no significant difference seen in mortality rates between the SG and CG (SMD = 0.53 [ 95% CI 0.13, 2.17] p = 0.61, I2 = 0%), in the time duration of postoperative mechanical ventilation between the SG and CG (SMD = -0.23 [95% CI -0.49, 0.03] p = 0.29, I2 = 19%), or PAP/AoP ratio between the SG and CG (SMD = -0.42 [95% CI -1.35, 0.51] P < 0.01, I2 = 90%). Based on our analysis, sildenafil has little to no effect in reducing postoperative morbidity and mortality due to PH in infants and children with CHD.

Cardiovascular risk in a contemporary cohort of patients with myeloproliferative neoplasms'.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are a group of disorders of clonal haemopoiesis associated with an inherent risk of arterial and venous thrombotic complications. The prevalence of thrombotic complications and the impact of cardiovascular risk factors (CVRFs) in contemporary patient cohorts within the current era of MPN treatments have not been completely defined. OBJECTIVES: We aim to characterise the cardiovascular risk of patients with MPN by identifying the prevalence of CVRFs and describing the pattern of thrombotic events. We also aim to utilise the QRISK3 algorithm, which is a validated model used to estimate an individual's risk of developing cardiovascular disease, to further phenotype this cohort of patients. METHODS: We perform a retrospective analysis on a single-centre cohort of 438 patients with MPN. RESULTS: MPN patients continue to carry a high burden of vascular morbidity with a prevalence of arterial thrombotic events in 15.8 % (69/438) and venous thrombotic events in 13.2 % (58/438) of the cohort. The novel use of the QRISK3 algorithm, which showed a mean score of 13.7 % across the MPN population, provides further evidence to suggest an increased cardiovascular risk in MPN patients. CONCLUSION: With an increased risk of cardiovascular disease in patients with MPN, we propose an integrated approach between primary and specialised healthcare services using risk stratification tools such as QRISK3, which will allow aggressive optimisation of CVRFs to prevent thrombosis and reduce the overall morbidity and mortality in patients with MPN.

Early Stage Breast Cancer: Does Histologic Subtype (Ductal vs. Lobular) Impact 5 Year Overall Survival?

Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1-T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan-Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77-0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients.

Time to treatment disparities in gastric cancer patients in the United States of America: a comprehensive retrospective analysis.

Introduction: Gastric cancer ranks as the 5th most prevalent cancer and the 4th leading cause of cancer-related deaths worldwide. Various treatment modalities, including surgical resection, chemotherapy, and radiotherapy, are available for gastric cancer patients. However, disparities related to age, sex, race, socioeconomic factors, insurance status, and demographic factors often lead to delayed time to treatment. Methods: In this retrospective study, conducted between 2004 and 2019, we utilized data from the National Cancer Database (NCDB) to investigate the factors contributing to disparities in the time to first treatment, surgery, chemotherapy, and radiotherapy among gastric cancer patients. Our analysis incorporated several variables, and statistical analysis was conducted to provide valuable insights into these disparities. Results: We observed notable disparities in the timing of treatment for various demographic groups, including age, sex, race, insurance status, geographic location, and facility type. These disparities include longer time to treatment in males (32.67 vs 30.75), Native Americans (35.10 vs 31.09 in Asians), low-income patients (32 vs 31.15), patients getting treatment in an academic setting (36.11 vs 29.61 in community setting), significantly longer time to chemotherapy in 70+ age group (51.13 vs 40.38 in <40 y age group), black race (55.81 vs 47.05 in whites), low income people (49.64 vs 46.74), significantly longer time to radiotherapy in females (101.61 vs 79.75), blacks and Asians (109.68 and 113.96 respectively vs 92.68 in Native Americans) etc. There are various other disparities in time to surgery, chemotherapy, and radiotherapy. Conclusions: Understanding these disparities is crucial in developing targeted strategies to improve timely access to appropriate treatments and enhance outcomes for gastric cancer patients. Future research with updated data and prospective study designs can provide a more comprehensive understanding of the factors influencing patient outcomes in gastric cancer.

Disparities in time to treatment initiation for rectal cancer patients: an analysis of demographic and socioeconomic factors.

Background: This study investigated demographic and socioeconomic factors contributing to disparities in the time to treatment for rectal cancer. Subgroup analysis based on age < 50 and ≥ 50 was performed to identify differences in time to treatment among young adults (age < 50) compared to older adults with rectal cancer. Methods: An analysis was performed using data from the National Cancer Database, spanning from 2004 to 2019. The study encompassed 281,849 patients diagnosed with rectal cancer. We compared time intervals from diagnosis to surgery, radiation, and chemotherapy, considering age, sex, race, and socioeconomic variables. Analyses were performed for the entire cohort and for two subgroups based on age (< 50 and ≥ 50). Results: Overall, Hispanic patients experienced longer times to surgery, radiation, and chemotherapy compared to non-Hispanic patients (surgery: 94.2 vs. 79.1 days, radiation: 65.0 vs. 55.6 days, chemotherapy: 56.4 vs. 47.8 days, all p < 0.001). Patients with private insurance had shorter times to any treatment (32.5 days) compared to those with government insurance or no insurance (30.6 and 32.5 days, respectively, p < 0.001). Black patients experienced longer wait times for both radiation (63.4 days) and chemotherapy (55.2 days) compared to White patients (54.9 days for radiation and 47.3 days for chemotherapy, both p < 0.001). Interestingly, patients treated at academic facilities had longer times to treatment in surgery, radiation, and chemotherapy compared to those treated at comprehensive and community facilities. When analyzed by age, many of the overall differences persisted despite the age stratification, suggesting that these disparities were driven more by demographic and socioeconomic variables rather than by age. Conclusion: Significant differences in the time to treatment for rectal cancer have been identified. Hispanic patients, individuals lacking private insurance, Black patients, and patients receiving care at academic facilities had the longest times to treatment. However, these differences were largely unaffected by the age (< 50 and ≥ 50) subgroup analysis. Further investigation into the causes of these disparities is warranted to develop effective strategies for reducing treatment gaps and enhancing overall care for rectal cancer patients.

A scoping review on integrated health campaigns for immunization in low- and middle-income countries.

Health campaign integration is a key implementation strategy outlined by the World Health Organization to achieve universal health coverage. This scoping review synthesizes the evidence on Integrated Health Campaigns (IHC) in the field of immunization in low- and middle-income countries (LMICs) regarding the most common strategies, facilitators and barriers. Four reviewers followed a systematic approach to identify, screen and analyse relevant articles. The team used three search engines (PubMed, Scopus and Google Scholar) to identify peer-reviewed journal articles as well as select institutional websites for grey literature publications. Full-text articles using any study design and across any time frame were included. Data were extracted following a predefined matrix, analysed deductively and presented in a narrative synthesis. Thirty articles (20 academic and 10 grey) were included in the final review. All studies included identified IHCs as effective when planning or implementation is integrated. The common strategies were: using resources efficiently in remote locations; using national immunization days to maximize impact; targeting specific age groups by selecting intervention sites that are frequented by that age group; building community ownership over the integrated program; and integrating programs that already share common elements. The key facilitators were: closing the gap between services and communities; planning, coordination and resource management both before and during integration; cost-effectiveness; and utilization of pre-existing infrastructure. The common barriers included seemingly optimized initial cost to appear feasible only in the short term and additional responsibilities on the field staff. This review finds IHCs a common practice in immunization and identifies gaps in evidence on evaluation; indicating the need for additional research. Strong evidence accounts IHCs to increase coverage, improve community acceptance of health services and strengthen the community models of health service delivery.

Role of laparoscopic surgery in the management of gallbladder cancer: Systematic review & meta-analysis.

BACKGROUND: This meta-analysis evaluates the safety and short-term oncological outcomes of laparoscopic vs. open surgery for gallbladder carcinoma(GBC). METHODS: Meta-analysis was performed on laparoscopic(LG) and open group(OG) studies. Data for survival outcomes were extracted from Kaplan-Meier curves and combined with Tierney's method to estimate hazard ratios(HRs) and 95% CIs. RESULTS: There was no significant difference in overall survival(HR: 1.01), disease-free survival(HR: 0.84), 30-day mortality(RR:1.10), overall recurrence(RR:0.93), intraoperative gallbladder violation(RR:1.17), operative time(WMD:8.32), number of patients receiving adjuvant chemotherapy(RR:1.06) and blood transfusion(RR: 0.81). A significant difference was seen in survival of T3 subgroup(HR:0.77) and number of lymph node dissections (LND)(WMD: 0.63) favoring OG, along with a decrease in postoperative complications(RR:0.65), greater incidence of R0 resections(RR:1.04), lower volume of intraoperative blood loss(WMD: 128.62), lower time in removing drainage tube(WMD: 1.35), shorter diet recovery time(WMD: 1.88), shorter hospital stay(WMD: 3.51), lower incidence of 90-day mortality(RR:0.49) favoring LG. A higher incidence of port-site recurrence(RR:1.99) was reported in LG. CONCLUSION: Laparoscopic surgery is non-inferior to the open approach in terms of oncological outcomes and has an improved rate of postoperative complications.

Modeling diabetic endothelial dysfunction with patient-specific induced pluripotent stem cells.

Diabetes is a known risk factor for various cardiovascular complications, mediated by endothelial dysfunction. Despite the high prevalence of this metabolic disorder, there is a lack of in vitro models that recapitulate the complexity of genetic and environmental factors associated with diabetic endothelial dysfunction. Here, we utilized human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) to develop in vitro models of diabetic endothelial dysfunction. We found that the diabetic phenotype was recapitulated in diabetic patient-derived iPSC-ECs, even in the absence of a diabetogenic environment. Subsequent exposure to culture conditions that mimic the diabetic clinical chemistry induced a diabetic phenotype in healthy iPSC-ECs but did not affect the already dysfunctional diabetic iPSC-ECs. RNA-seq analysis revealed extensive transcriptome-wide differences between cells derived from healthy individuals and diabetic patients. The in vitro disease models were used as a screening platform which identified angiotensin receptor blockers (ARBs) that improved endothelial function in vitro for each patient. In summary, we present in vitro models of diabetic endothelial dysfunction using iPSC technology, taking into account the complexity of genetic and environmental factors in the metabolic disorder. Our study provides novel insights into the pathophysiology of diabetic endothelial dysfunction and highlights the potential of iPSC-based models for drug discovery and personalized medicine.

Inequities in Time to Treat Thyroid Cancer.

BACKGROUND/AIM: The purpose of this study was to determine socioeconomic and demographic factors which may contribute to inequities in time to treat thyroid cancer. PATIENTS AND METHODS: We used data from the National Cancer Database, 2004-2019, to conduct an analysis of thyroid cancer patients. All (434,083) patients with thyroid cancer, including papillary (395,598), follicular (23,494), medullary (7,638), and anaplastic (7,353) types were included. We compared the wait time from diagnosis to first treatment, surgery, radiotherapy, and chemotherapy for patients based on age, race, sex, location, and socioeconomic status (SES). RESULTS: A total of 434,083 patients with thyroid cancer were included. Hispanic patients had significantly longer wait times to all treatments compared to non-Hispanic patients (first treatment 33.44 vs. 20.45 days, surgery 40.06 vs. 26.49 days, radiotherapy 114.68 vs. 96.42 days, chemotherapy 92.70 vs. 58.71 days). Uninsured patients, patients at academic facilities, and patients in metropolitan areas also had the longest wait times to treatment. CONCLUSION: This study identified multiple disparities related to SES and demographics that correspond to delays in time to treatment. It is crucial that this topic is investigated further to help mitigate these incongruities in thyroid cancer care in the future.

Sociodemographic Barriers to the Timely Treatment of Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic cancer has a high mortality rate and timely treatment is imperative for favorable patient outcomes. This retrospective study aimed to identify disparities in time to treatment for pancreatic cancer based on sociodemographic factors. PATIENTS AND METHODS: The study used the National Cancer Database from 2004 to 2019. A total of 423,482 patients with pancreatic cancer were included in the study. Time to first treatment, surgery, radiation, and chemotherapy were analyzed in the context of age, sex, race, Hispanic origin, insurance status, income, facility type, geographic setting, grade, stage, and Charlson-Deyo Comorbidity score (CDC). RESULTS: All sociodemographic factors included were found to be significantly associated with disparities for time to treatment in at least one of the categories studied. Minorities, treatment at academic facilities, and patients with a high CDC score had consistently longer times to all treatment classifications. CONCLUSION: The analyzed sociodemographic factors affected time to pancreatic cancer treatment. Disparities in time to treatment for pancreatic cancer must be studied and understood to ameliorate the impact this cancer has on society and assure the best possible care for all communities.