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The proportion of cancers of genital tract origin in females ranges from 22.4% to 55.8% in India; thus posing a major health problem. The first step in controlling the cancer burden in any population is to collect information about its salient features in that particular cohort of patients. This study was performed to ascertain the profile of female genital tract malignancies reported at our center regarding the relative frequency of involvement of various sites, age and symptoms at presentation and histological subtypes.All the confirmed cases of female genital tract malignancies received in the Department of Pathology were studied for a period of 2 years from November 2008 to October 2010.A total of 175 cases were reported. The anatomic distributions were: cervix 123 (70.3%), uterus 11 (6.3%), ovary 30 (17.1%), vagina 4 (2.3%), vulva 5 (2.9%) and fallopian tube 2 (1.1%). The mean ages of women diagnosed with these cancers were: cervix (51.1 years), uterus (54.5 years), ovary (46.5 years), vagina (57 years), vulva (54.5 years) and fallopian tube (49.5 years). Women with cervical and uterine malignancies presented commonly with bleeding per vaginum; while those with ovarian malignancies presented mostly with abdominal mass. Women with vaginal and vulval malignancy presented with ulcers and masses. The most common histological subtypes at different sites were; Cervix: Squamous cell carcinoma (SCC) (87%); Uterus: Endometrioid adenocarcinoma (81.8%); Ovary: Serous cystadenocarcinoma (53.3%); Vagina: SCC (75%); Vulva: SCC (60%) and Fallopian tube (50% adenocarcinoma and 50 % metastatic carcinoma).As female genital tract malignancies form a huge burden of morbidity and mortality in India, there is a need to establish better screening programmes aimed at early detection and educate the public regarding the risk factors as well as early symptoms of the disease so that people can adapt appropriate behaviour.

Background: Tetralogy of Fallot (TOF) is one of the most common congenital cardiac defect. In patients with small PV annulus, it has to be augmented to certain diameter by cutting annulus. In these cases, transannular patch is used free PR is inevitable. Free PR with transannular patch ultimately leads to RV dilatation, dysfunction, arrhythmia and failure with time. Monocuspid reconstruction of PV is commonly practiced in many centers but its long-term outcome is poor though it helps to achieve a less stormy ICU course. Modified monocusp or bicuspid PV reconstruction is a good choice where 0.1mm PTFE patch is used. Objectives: We are presenting the results of bicuspid PV reconstruction using a 0.1mm PTFE patch as a method of RVOT reconstruction in repair of TOF with transannular patch. Methods: A total, 42 patients diagnosed as TOF were treated from January 2016 to October 2020. Age range 18 months to 35 years, weighing 10 kg to 70 kg. 38 patients had TOF, 4 had DORV with PS. The transannular patch was followed by implantation of a 0.1-mm PTFE modified monocusp valve using posterior fixation. Results: Among total patients 28 were male and 14 were female. Mean age 9.58±5.6 yrs. Bypass time was 187±31 min, cross-clamp time 123.63±25.42 min. Out of 42 patients, PR gradient was trivial in 7(16.67%), mild in 31(73.1%), moderate in 4(9.52%) patients. First, a follow-up echocardiogram revealed no significant deterioration of PR gradient. ICU stay was 89±32.6 hours and mean hospital stay 11.48±2.1 days. Conclusion: Initial results using a transannular patch with a modified monocusp valve to repair the outflow tract in cases of Tetralogy of Fallot were excellent. There were only a slight pressure gradient and mild regurgitation in most of the cases. DS (Child) H J 2020; 36(2): 114-119

The surgical treatment of pancreas ductal adenocarcinoma (PDAC) is plagued by high rates of distant recurrences despite complete resection, highlighting the importance of systemic therapy. Historically, patients with PDAC have been treated with postoperative therapy, but this sequencing strategy can be associated with the inability to complete therapy due to perioperative complications and prolonged recovery. In addition, a subset of patients progress early, irrespective of whether surgery is performed, highlighting the systemic nature of this disease. Preoperative therapy has increasingly been utilized in clinical practice, but studies examining its benefits are limited. In this Landmark Series, we will review seminal studies for resectable and borderline resectable PDAC.

Objective: The objective of the study was to monitor the adverse drug reactions (A.D.Rs.) associated with antihypertensive drugs. Methods: All patients coming to the department with blood pressure systolic above 120 mmHg and diastolic above 90 mmHg and prescribed hypertensives will be screened for the study. Results and Discussion: A total of 136 patients were observed during the study. Out of 136 patients, 23 (17%) A.D.Rs. were recorded. A study conducted by Ramesh et al. in the Indian capital reports that 22.3% of the patients experienced A.D.Rs. Conclusion: Furthermore, any appearance of A.D.Rs. due to side effects of the drugs or due to bad control and patients non-compliance, it was treated mainly by decreasing the doses of the drugs, switching them to another active substance from the same pharmacological group, or by adding more active substances from different pharmacological groups in lower dosages to achieve the B.P goals.

BACKGROUND In 2004, the European Study Group for Pancreatic Cancer (ESPAC)-1 long-term data concluded that adjuvant chemotherapy provided a survival benefit for patients with pancreatic ductal adenocarcinoma (PDAC), whereas adjuvant chemoradiation was associated with worse overall survival. In this study, we investigated how long it took for US practice patterns to change following this trial. METHODS The National Cancer Database was used to identify patients with stage I-III PDAC who underwent R0 or R1 resection followed by adjuvant chemotherapy or chemoradiation between 1998 and 2015. A multivariate analysis was performed to determine predictors of receiving adjuvant chemoradiation in the post-ESPAC-1 era. RESULTS Between 1998 and 2015, adjuvant chemotherapy use increased from 2.9% to 51.6%, whereas adjuvant chemoradiation decreased from 49.5% to 22.9%. In 2010, adjuvant chemotherapy utilization surpassed that of chemoradiation. For patients diagnosed in the post-ESPAC-1 era, adjuvant chemotherapy (n = 7733) and chemoradiation (n = 6969) groups were compared. Patients who underwent adjuvant chemoradiation were younger, had private insurance, underwent surgery at nonacademic centers, and had more pathologically advanced cancers (all P

BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1–4)]. ERCP was more common in those with obstructed pancreatic duct (p=0.0009), pancreas divisum (p=0.0009), prior pancreatic surgery (p=0.005), and longer disease duration (p=0.004). A greater number of ERCPs was associated with disease duration (p

Background We recently reported prostate apoptosis response 4 (Par-4), a potential tumor suppressor protein restrains epithelial-mesenchymal transition (EMT) properties and promotes mesenchymal-epithelial transition (MET) in invasive cancer cells by repressing Twist-1 promoter activity. Here, we demonstrate that genetic as well as pharmacological modulation of Par-4 by NGD16 (a small molecule antimetastatic agent), limits EMT-induced chemoresistance in aggressive cancer cells by suppressing MDM-2, a downstream effector of Twist-1. Methods Matrigel invasion assay, gelatin degradation assay, cell scattering assay, MTT assay and colony formation assay were used to study the proliferation and migration abilities of invasive cancer cells. Immunoblotting, immunocytochemistry, and immunoprecipitation analysis were utilized for determining protein expression and protein-protein interaction. 4T1 aggressive mouse carcinoma model was employed to evaluate tumor growth and lung metastasis. Results Treatment of gemcitabine (nucleoside analogue anticancer agent) to pancreatic cancer (Panc-1, MiaPaca-2) and breast cancer (MDA-MB-231) cells amplified MDM-2 expression along with increase in EMT properties. Conversely, NGD16 boosted expression of tumor suppressor Par-4 and inhibited invasion and migration abilities of these cells. Moreover, induction of Par-4 effectively diminished MDM-2 along with pro-EMT markers, whereas, augmented the expression of epithelial markers. Furthermore, siRNA-mediated silencing of Par-4 divulged that NGD16 exerts its EMT inhibitory effects in a Par-4-dependent manner. Mechanistically, Par-4 activation provokes p53 by disrupting MDM-2-p53 interaction, which restored epithelial characteristics in cancer cells. Additionally, partial knockdown of MDM-2 through siRNA pronounced the anti-proliferative and anti-invasive effects of NGD16. Finally, NGD16 efficiently inhibited tumor growth and lung metastasis in mouse mammary carcinoma model without showing any undesirable effects. Conclusion Our findings unveil Par-4 as a key therapeutic target and NGD16 (the pharmacological modulator of Par-4) are potential tools to suppress EMT and associated chemoresistance, which could be exploited clinically for the treatment of aggressive cancers.

Objectives: The objective was to compare the efficiency and assess postoperative complications of 2.00 mm unicortical locking plates and three-dimensional (3D) plates in surgical correction of uncomplicated mandibular fracture. Materials and Methods: A prospective cohort study of twenty patients of uncomplicated mandibular fractures, who were operated either by noncompression unicortical 2-mm locking mini-plate or by noncompression unicortical 2-mm 3D mini-plate, were enrolled and followed up for the study outcomes such as operative time, postoperative infection, and postoperative occlusion. Results: Majority of the patients (90%) were male who had road traffic accident. In 80% of cases, mandibular fracture site was parasymphysis. The mean operating time for 3D plates (43.20 min) was significantly lower than that for locking plates (54.82 min), P < 0.001. All cases operated by 3D plates compared to 60% by locking mini-plates did not need intermaxillary fixation, P = 0.025. The 80% of cases operated by 3D plates did not require postoperative occlusion correction compared to 30% in another group, P = 0.01. For other parameters such as postoperative sensory disturbance, postoperative infection, incidence tooth damage, vertical displacement of mandible, feeling of plate after platting, and chewing efficiency after 1 week, there were no statistical significant differences between the two groups. Conclusions: The outcome of 2.0mm 3D mini-plate is better in terms of operating time required, post-operative need of intermaxillary fixation and occlusal correction. While the outcome is similar to the use of non-compression unicortical 2.00mm locking miniplate in parameters like infection rate and incidence of tooth damage etc.

Background Level 1 evidence for multimodal treatment of resectable gastric adenocarcinoma from the Intergroup 0116 (2001) and MAGIC (2006) trials demonstrated survival benefit of adjuvant chemoradiation (CRT) and perioperative chemotherapy, respectively. We evaluated the adoption of evidence-based treatment in the post-MAGIC era and its impact on survival. Methods A total of 7058 patients with resectable gastric adenocarcinoma undergoing definitive surgical resection between 2004 and 2015 were analyzed using the National Cancer Database. Results Over the study period, the proportion of patients receiving adjuvant CRT decreased from 19.1% to 9.1%, while perioperative chemotherapy increased from 1.9% to 28.6%. Utilization of perioperative chemotherapy surpassed adjuvant CRT in 2011. Evidence-based treatment (either perioperative chemotherapy or adjuvant CRT) had better overall survival (OS) than other treatments for clinical stage II–III patients (p < 0.05). On multivariate analysis of the whole study period, evidence-based treatments were associated with better OS (HR 0.67 [0.60–0.74], p < 0.05). Only 360/1262 (28.5%) patients in the perioperative chemotherapy group completed postoperative therapy, which was associated with improved OS (p < 0.05). For clinical stage III patients (n = 2402), only 806 (33.6%) received evidence-based treatment, while 487 (22.2%) underwent surgery alone. On multivariate analysis of these patients between 2010 and 2015, both perioperative chemotherapy (HR 0.49 [0.35–0.68]) and adjuvant CRT (HR 0.31 [0.21–0.44]) were associated with better OS than surgery alone (p < 0.05). Conclusions Since the INT-0116 and MAGIC trials, utilization of evidence-based treatments for resectable gastric adenocarcinoma has increased, with perioperative chemotherapy surpassing adjuvant CRT as the preferred practice. However, overall utilization of these regimens remains quite low nationally despite association with improved OS.

Background:An increasing number of newborn children in numerous nations are enrolled in early childhood education programs, and instructors, in this way, assume a focal job in invigorating language improvement in these youthful kids. Kids with language issues are found to have a higher risk for future scholarly challenges and learning inabilities. Language advancement among kids is an intricate procedure and vital for correspondence. The shortcomings in the utilization of grammatical structures may lessen the useful utilization of language for verbally expressive kids with autism spectrum disorder and exacerbate troubles with academic and social expertise advancement.Results:FOXP2, the single principal gene connected to a speech and language issue, is significant for the right execution of complex motor behaviors used for speech. In any case, changes in FOXP2 lead to a speech/language issue portrayed by childhood apraxia of speech. These days, language learning is fundamentally required for kids who need to move to different nations to pursue the instructive frameworks and be helpful individuals or residents of those nations.Conclusion:The purpose of this study was to explore the role of FOXP2 in language disorder and its management for children’s language and communication development.

Objectives The goal of this study was to compare outcomes of patients with borderline and resectable pancreatic cancer treated with neoadjuvant stereotactic body radiation therapy (SBRT) versus fractionated chemoradiation. Methods Patients with borderline or resectable pancreatic cancer treated with neoadjuvant intent between November 2011 and December 2017 were reviewed. The SBRT volume/dose was 33 Gy in 5 fractions to gross tumor plus abutting vessel with or without 25 Gy in 5 fractions to pancreatic head/body and celiac/superior mesenteric artery. Fractionated chemoradiation volume/dose was 50.4 Gy in 28 fractions to gross tumor, superior mesenteric/celiac arteries, and enlarged lymph nodes with concurrent bolus 5-FU, leucovorin, oxaliplatin, irinotecan or gemcitabine/nab-paclitaxel. Failure patterns, local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival were assessed. Results Forty-three patients were reviewed (18 SBRTs and 25 fractionated). Among patients who underwent resection, patients treated with fractionated chemoradiation had improved LRFS (12-month LRFS, 86% vs 62%, P = 0.003) and PFS (median PFS, 23 months vs 11 months, P = 0.006) compared with SBRT. There was no difference in overall survival. Conclusions Stereotactic body radiation therapy may result in inferior LRFS and PFS compared with fractionated chemoradiation, likely because of under coverage of high-risk vascular targets.

Background: Gastric cancer accounts for many cancer-related deaths, is one of the top leading cause of cancer-associated mortality. Tumor staging and classification depends upon histological, immune histochemical tests along with the radiological imaging. In the preoperative T staging of gastric cancer, Magnetic Resonance Imaging (MRI) has become principal attention in recent years. Aim: Evaluating the accuracy of MRI in the preoperative T staging of gastric cancer vis-a-vis post-operative pathological staging. Methods: A total of 37 patients were initially taken in our study, out of which 13 patients were excluded as they underwent neo adjuvant chemoradiotherapy for the down staging of the tumor. The 24 patients became the sample size of our study and their magnetic resonance imaging (MRI) T stage was correlated with pathological T-stage. Results: The diagnostic accuracy of T1 stage by MRI was 87.5%, with 94.7% specificity and 60% sensitivity (n=24, κ -value = 0.58; P-value

Drug induced resistance is a widespread problem in the clinical management of cancer. Cancer cells, when exposed to cytotoxic drugs, can reprogram their cellular machinery and resist cell death. Evasion of cell death mechanisms, such as apoptosis and necroptosis, are part of a transcriptional reprogramming that cancer cells utilize to mediate cytotoxic threats. An additional strategy adopted by cancer cells to resist cell death is to initiate the epithelial to mesenchymal transition (EMT) program. EMT is a trans-differentiation process which facilitates a motile phenotype in cancer cells which can be induced when cells are challenged by specific classes of cytotoxic drugs. Induction of EMT in malignant cells also results in drug resistance. In this setting, therapy-induced senescence (TIS), an enduring “proliferative arrest”, serves as an alternate approach against cancer because cancer cells remain susceptible to induced senescence. The molecular processes of senescence have proved challenging to understand. Senescence has previously been described solely as a tumor-suppressive mechanism; however, recent evidences suggest that senescence-associated secretory phenotype (SASP) can contribute to tumor progression. SASP has also been identified to contribute to EMT induction. Even though the causes of senescence and EMT induction can be wholly different from each other, a functional link between EMT and senescence is still obscure. In this review, we summarize the evidence of potential cross-talk between EMT and senescence while highlighting some of the most commonly identified molecular players. This review will shed light on these two intertwined and highly conserved cellular process, while providing background of the therapeutic implications of these processes.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Context Road traffic injuries is estimated to be the ninth leading cause of death across all age groups globally. People in need of trauma care, after a road crash, are most likely to survive if they receive definitive care within the first hour (Golden hour) after the crash. Essential prehospital care includes prompt communication, treatment, and transport of injured people to formal healthcare facilities. Aims To assess the availability and utilization pattern of existing facilities for post-crash emergency care in Aligarh. Settings and design The present study was undertaken on two National highways- NH-91 and NH-93 and the connecting bypass roads of Aligarh district of Uttar Pradesh. Subjects and methods All the individuals who met road traffic accident (RTA) between the earmarked areas from 1st October, 2018 to 30th September, 2019 and reported for treatment (either on their own or brought by relatives, passersby, ambulance or police) to the selected hospitals were included in the study. Statistical analysis used Data presented in the form of frequency tables and percentages. Results Out of 665 patients interviewed during the study period, 556 (83.61%) patients were males and 109 (16.39%) were females with M: F ratio been 5.10:1. Among the first responders, 448 (67.36%) were lay persons and 42 (6.31%) were police personnel. 261 (39.25%) of patients received help within 10-30 min of RTA. Use of toll-free no. was limited to 265 (39.84%) patients. Ambulance was the mode of transport in 155 (23.30%) of RTA cases. 589 (88.58%) of patients reported to Government hospitals. Conclusions Post-crash emergency care is in nascent stage in Aligarh district of Uttar Pradesh. Toll free numbers and ambulances are available but proper utilization and quality of care is lacking. Lay person is the most important personnel in improving the post-crash care.

Recurrent molar pregnancy is very rare. In this case report, we highlight a case of a patient who experienced five recurrent molar pregnancies without an intervening normal pregnancy. A 22-year-old patient was admitted to our labour room with a fifth consecutive molar pregnancy. The patient underwent suction and evacuation and was followed up with serial serum human chorionic gonadotropin (beta-hCG) estimation. The patient did not require chemotherapy. Karyotype of the patient and her husband was normal. Nonetheless, the couple was counselled for adoption.

Background:Phytochemicals are a significant piece of conventional prescription and have been researched in detail for conceivable consideration in current drug discovery. Medications and plants are firmly identified for traditional prescriptions and ethnomedicines that are basically arranged from plants. Recognizing the medical advantages of phytochemicals is of fundamental advancement in medication and useful sustenance improvement. Secondary metabolites of different plants have been customarily used for the improvement of human wellbeing. The phytochemicals are diets rich, which can upgrade neuroplasticity and protection from neurodegeneration.Results:Phytochemicals keep on entering clinical preliminaries or provide leads for the synthesis of medicinal agents. Phytochemicals are a great extent cancer prevention agents in nature at lower concentrations and under favorable cell conditions that adequately avoid the oxidation of different molecules that have an ability to produce free radicals and thus protect the body.Conclusion:The purpose of this review is to describe the use of phytochemicals against cancer and Alzheimer’s disease treatment.

Technological advances have made it possible to offer home-based chemotherapy to patients without health care professionals being present. Prior studies on effects of home-based treatment lack inclusion of patients with hematologic malignancies. We present data from a multicenter single-arm feasibility and safety study of home-based intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia and their quality of life and psychological wellbeing. This national study included patients from six sites in Denmark who received intensive chemotherapy on programmed CADD Solis infusion pumps through a central venous catheter and were also managed as outpatients during treatment-induced pancytopenia. Data are presented from 104 patients, receiving 272 treatments with 1.096 (mean 4.57, SD 3.0) home infusion days out of 1.644 treatment days (67 %). Sixty-two of 168 (36.9 %) reinduction and consolidation treatment cycles ensuing pancytopenia phases were solely handled in the outpatient clinic. Patients reported high satisfaction with home-based treatment, which had a positive influence on their ability to be involved in their treatment and be socially and physically active. No unexpected events occurred during the intervention. Overall, patients improved in all quality of life outcomes over time. Home-based intensive chemotherapy treatment was feasible and safe in this population. ClinicalTrials.gov identifier: NCT04904211

Summary: Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of Treg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic Treg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling Treg cell development. However, MAZR-deficient Treg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral Treg cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a Treg cell-intrinsic transcriptional network that modulates Treg cell development. : FOXP3+ Treg cells are essential for maintaining tolerance and immune homeostasis. Andersen et al. reveal that MAZR is an important factor in regulating the delicate balance of Treg cell generation and report that MAZR expression levels play a key role in controlling Treg cell development and differentiation. Keywords: MAZR, PATZ1, FOXP3, regulatory T cells, Treg, DSS-induced colitis

Surgeon-led clinical trials have defined the standard of care for locoregional pancreatic cancer to date. The infrastructure and collaborative nature of cooperative oncology groups offer many advantages, such as providing an ideal mechanism through which multidisciplinary pancreatic cancer trials are performed. As key members of the treatment team, surgeons bring experience and expertise to the design of surgical and multidisciplinary trials and are uniquely poised to be leaders of future pancreatic cancer trials.

Limitations of radiofrequency ablation (RFA) treatment for nonresectable liver cancer could potentially be overcome by monitoring and controlling RFA to confirm complete treatment. Echo decorrelation imaging has been shown to predict local thermal ablation and to successfully control ablation in animal liver and tumor tissue, both ex vivo and in vivo. Toward translation of this monitoring and control approach to clinical liver tumor ablation, this study investigated control of RFA in ex vivo human liver tissue using 3D echo decorrelation imaging. Human liver tissue, including postmortem normal liver as well as explanted cirrhotic and fatty liver, was ablated using a clinical RFA system. During ablation, 3D echo decorrelation images were constructed from paired sequential volumes of acquired echo data. For controlled RFA trials, ablation was ceased automatically after cumulative echo decorrelation, spatially averaged within a spherical ROI matching the planned ablation zone, exceeded a predetermined threshold. This control algorithm was tested in $N=6$ controlled ablation trials, of which 5 attained the predetermined decorrelation threshold. 3D echo decorrelation maps were compared to segmented ablation zones, using receiver operating characteristic (ROC) curve analysis. To assess the effect of image-based feedback control on treatment reliability, ablation volumes and rates, as well as Dice coefficients for measured vs. targeted ablation zones, were statistically compared for controlled vs. uncontrolled trials. Results suggest potential for 3D echo decorrelation imaging as a monitoring and control approach for clinical ablation of liver tumors.

The skeletal muscle (SM) is the largest organ in the body and has tremendous regenerative power due to its myogenic stem cell population. Myostatin (MSTN), a protein produced by SM, is released into the bloodstream and is responsible for age-related reduced muscle fiber development. The objective of this study was to identify the natural compounds that inhibit MSTN with therapeutic potential for the management of age-related disorders, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 natural compounds was performed, and dithymoquinone (DTQ) was found to inhibit MSTN with a binding free energy of −7.40 kcal/mol. Furthermore, the docking results showed that DTQ reduced the binding interaction between MSTN and its receptor, activin receptor type-2B (ActR2B). The global energy of MSTN-ActR2B was found to be reduced from −47.75 to −40.45 by DTQ. The stability of the DTQ–MSTN complex was subjected to a molecular dynamics analysis for up to 100 ns to check the stability of the complex using RMSD, RMSF, Rg, SASA, and H-bond number. The complex was found to be stable after 10 ns to the end of the simulation. These results suggest that DTQ blocks MSTN signaling through ActR2B and that it has potential use as a muscle growth-promoting agent during the aging process.

Pleomorphic adenoma (PA), also called mixed tumor, is the most common benign tumor of the salivary glands that mostly occurs in the parotid or submandibular glands but may also occur in the minor salivary glands that are distributed throughout the oral cavity. The common sites of PA of the minor salivary glands are the palates followed by lips and cheeks. Surgical removal with adequate margins is the principal treatment. We present a case of PA (arising from the minor salivary gland of the upper lip) - a rare site in a 65-year-old female who presented with a swelling upper lip of 2-year duration. Fine-needle aspiration cytology of the swelling revealed PA which was confirmed by histopathological examination after complete excision of the swelling.

Background Healthy vaginal microbiome is dominated by Lactobacilli, which constitute a strong line of defense against vaginal diseases like Bacterial vaginosis (BV). Bacterial Vaginosis is a polymicrobial disease characterized by gradual replacement of predominant population of Lactobacillus with anaerobic uropathogens such as Gardnerella vaginalis (GV), Prevotella and Mobiluncus spp. Due to antibiotic resistance in these pathogens, Lactobacillus spp. have been given attention in the prophylaxis and prevention of infections such as, urinary tract infections, genital infections and BV. Current study describes role of L. reuteri in reducing BV in a GV induced BV murine model. In addition, immunomodulatory effects of L. reuteri were assessed by analyzing gene expression of inflammatory and anti-inflammatory markers by real time PCR in vaginal tissue.Methods Study was divided into two parts. In phase 1, two groups of mice were intravaginally administered with L. reuteri and GV at a dose of 1 x 10 6 CFUml -1 and 5 x 10 5 CFUml -1 respectively and their colonization was confirmed by re-isolation of these strains in vaginal washes. In phase 2, prophylactic efficacy of L. reuteri in GV induced BV mice model were observed by considering clinical scoring, re-isolation frequency, bacterial load, change in epithelium of vaginal tissue and tissue inflammatory and anti-inflammatory markers.Results A significant reduction in clinical scores and re-isolation frequency was noticed in GV challenged pre- L. reuteri colonized animals (prophylactic group). On 10 th day, L. reuteri restricted the growth of GV and kept its count significantly lower than in GV positive control group. Reduction in epithelial thickness and exfoliation was noticed in histological sections of treated group as compare to that in positive control group. In addition to their antimicrobial potential against GV, a depletion in IL-6, IL-1β and elevation in IFN-γ was noticed in L. reuteri treated GV challenged mice.Conclusions Based on aforementioned findings, it is concluded that L. reuteri could be considered a natural candidate for therapies of female genital infections.

In 2021, pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer deaths in the United States. This is largely due to a lack of symptoms and limited treatment options, which extend survival by only a few weeks. There is thus an urgent need to develop new therapies effective against PDAC. Previously, we have shown that the growth of PDAC cells is suppressed when they are co-implanted with RabMab1, a rabbit monoclonal antibody specific for human alternatively spliced tissue factor (asTF). Here, we report on humanization of RabMab1, evaluation of its binding characteristics, and assessment of its in vivo properties. hRabMab1 binds asTF with a KD in the picomolar range; suppresses the migration of high-grade Pt45.P1 cells in Boyden chamber assays; has a long half-life in circulation (~ 5 weeks); and significantly slows the growth of pre-formed orthotopic Pt45.P1 tumors in athymic nude mice when administered intravenously. Immunohistochemical analysis of tumor tissue demonstrates the suppression of i) PDAC cell proliferation, ii) macrophage infiltration, and iii) neovascularization, whereas RNAseq analysis of tumor tissue reveals the suppression of pathways that promote cell division and focal adhesion. This is the first proof-of-concept study whereby a novel biologic targeting asTF has been investigated as a systemically administered single agent, with encouraging results. Given that hRabMab1 has a favorable PK profile and is able to suppress the growth of human PDAC cells in vivo, it comprises a promising candidate for further clinical development.

Tine Bichel Lauritsen,1 Jan Maxwell Nørgaard,1 Kirsten Grønbæk,2– 4 Anders Pommer Vallentin,5 Syed Azhar Ahmad,6 Louise Hur Hannig,7 Marianne Tang Severinsen,8,9 Kasper Adelborg,10,11 Lene Sofie Granfeldt Østgård11,12 1Department of Hematology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Hematology, Rigshospitalet, Copenhagen, Denmark; 3Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark; 4Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 5Zealand University Hospital, Roskilde, Denmark; 6Department of Hematology, Herlev Hospital, Herlev, Denmark; 7Department of Hematology, Vejle Hospital, Vejle, Denmark; 8Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; 9Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 10Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; 11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 12Department of Hematology, Odense University Hospital, Odense, DenmarkCorrespondence: Tine Bichel LauritsenDepartment of Hematology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, 8200 Email tinelaur@rm.dkBackground: The Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for epidemiological research and the quality of registered variables remains to be investigated.Objective: To describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records.Methods: We performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010– 2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard.Results: Overall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88– 95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after.Conclusion: In this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS.Keywords: myelodysplastic syndromes, cohort, validation, accuracy, database

Temporomandibular joint disorders (TMDs) encompass a wide array of ailments affecting the temporomandibular joint (TMJ), muscles of mastication, and the allied structural framework. Myofascial pain, internal derangement of the joint, and degenerative joint diseases constitute the majority of TMDs. TMDs usually have a multifactorial etiology, and treatment modalities range from conservative therapies to surgical interventions. Low-level laser therapy (LLLT) has evolved as an efficient non-invasive therapeutic modality in TMDs. Previously conducted systematic reviews and meta-analyses have shown variable results regarding the efficiency of LLLT in TMJ disorder patients. Hence, this systematic review was carried out as an attempt to evaluate the efficacy of LLLT in the treatment of temporomandibular joint disorder patients.

Type 2 diabetes mellitus (T2DM) is an increasing global public health problem, and its prevalence is expected to rise in coming decades. Dipeptidyl peptidase-4 (DPP-4) is a therapeutic target for the management of T2DM, and its inhibitors prevent the degradation of glucose-dependent insulinotropic peptide and glucagon-like peptide 1, and thus, maintain their endogenous levels and lower blood glucose levels. Various medicinal plant extracts and isolated bioactive compounds exhibit DPP-4 inhibitory activity. In this review, we discussed different natural sources that have been shown to have anti-diabetic efficacy with a particular emphasis on DPP-4 inhibition. Furthermore, the effect of DPP-4 inhibition on pancreatic beta cell function, skeletal muscle function, and the glucose-lowering mechanisms were also discussed. We believe that scientists looking for novel compounds with therapeutic promise against T2DM will be able to develop antidiabetic drugs using these natural sources.

Aim or purpose: To present a modified technique of trabeculectomy. Design: Ahmad’s modified trabeculectomy technique aims to utilize subtle modifications to the classical trabeculectomy technique in order to achieve a better filtering bleb leading to lesser complications. Methods: Retrospective interventional case series. Results: Thirty-four patients underwent this surgery. There was a significant difference in the preoperative and postoperative median intraocular pressure (IOP; z = 3.928; p < 0.001). The postoperative IOP (median = 12) was significantly lower than the preoperative IOP (median = 28; interquartile range = 9). Conclusion: This modification can prove to be an effective method to reduce IOP with minimal complications.

Objective: To prospectively validate the WINROP (Weight, Insulin-like growth factor 1, Neonatal, Retinopathy of Prematurity) screening algorithm (www.winrop.com) based on longitudinal measurements of neonatal body weights in predicting the development of severe retinopathy of prematurity (ROP) among preterm infants admitted to the neonatal intensive care unit of a tertiary care center in East Malaysia. Methods: All premature infants of less than 32 weeks gestational age (GA) were included in this cohort. Their body weight was measured weekly from birth to 36 weeks postmenstrual age and entered into the computer-based surveillance system: WINROP. Infants were then classified by the system into high- or low-risk alarm group. The retinopathy findings were recorded according to Early Treatment for ROP criteria. However, the screening and management of infants were done according to the recommendations of the Continuous Practice Guidelines, Ministry of Health, Malaysia. The team members involved in screening and those recording the findings were kept blinded from each other. Results: A total of 151 infants with median GA at birth of 30 weeks (interquartile range [IQR] Å} 2.1) and mean birth weight of 1,264 g (standard deviation Å} 271) were analyzed. High-risk alarm was signaled in 85 (56.3%) infants and 9 (6.6%) infants developed type 1 ROP. One infant in the low-risk alarm group developed type 1 ROP requiring laser retinal photocoagulation. The median time lag from the high-risk alarm signal to the development of type 1 ROP was 10.4 (IQR Å} 8.4) weeks. Conclusion: In this cohort, the WINROP algorithm had a sensitivity of 90%, with negative predictive value of 98.5% (95% confidence interval) for detecting infants with type 1 ROP and was able to predict infants with ROP earlier than their due screening date. This study shows that a modified version of the WINROP algorithm aimed at specific populations may improve the outcome of this technique.

Pancreatectomy with islet autotransplantation (IAT) is a treatment option for children with debilitating chronic pancreatitis. Sterility cultures from preservation solutions are often positive, yet their impact has not been well studied in children. A retrospective review of all patients who underwent IAT from 2015 to 2018 at a single institution was performed. Sterility culture data were obtained from both the pancreas transport and islet transplant media. All patients received prophylactic perioperative meropenem and vancomycin for 72 h per our protocol. If cultures resulted positive, antibiotics were extended for a total of 7 days. Primary outcomes were postoperative fever and 30-day infectious complications. Forty-one patients underwent IAT during the study period. Seventeen (41.5 %) patients had negative cultures of both the transport and transplant media, while 24 (58.5 %) patients had a positive culture from either sample. Of these patients, 13 (31.7 %) were positive in both, 10 (24.4 %) were positive in only the transport media, and 1 (2.4 %) was positive in only the transplant media. Patients with positive transplant media were similar with regard to age, gender, etiology, and disease duration compared to those with negative transplant media (all p > 0.05), but the positive group was more likely to have a pancreatic stent in place at the time of surgery (38.5 % vs. 4.2 %, p = 0.01). The overall postoperative infectious complication rate was 31.2 % (n = 13). No difference was detected between the transplant positive and negative culture groups in postoperative fever or 30-day infectious complications (p > 0.05 for each). An existing pancreatic stent at the time of pancreatectomy with IAT is a risk factor for positive sterility cultures. However, positive islet transplant media culture was not associated with increased risk of post-IAT infection or morbidity in the setting of an empiric antibiotic protocol. Future work is necessary to study the optimal perioperative antibiotic regimen in pediatric IAT.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

Introduction: Breast carcinoma is a heterogenous disorder in which the treatment modality should be based on a risk assessment approach and only patients with higher relative risk of recurrence and distant metastasis should be the appropriate candidates for adjuvant therapy. This is where role of prognostic variables like Ki-67 and p53 immunoexpression as biomarkers of proliferative activity of tumor cells becomes important. Aims and Objectives: The aim of this study was to evaluate the significance of Ki-67 and p53 immunoexpression as prognostic biomarkers in breast carcinoma patients with positive axillary lymph nodes. Material and Methods: A total of 182 breast cancer patients were included in the study, assessed for various clinicopathological characteristics and after receiving the mastectomy/lobectomy specimen, tissue sections about 1cm thick were taken from representative areas, processed in an automated tissue processor (Histokinette) and simultaneously stained for routine hematoxylin and eosin stain along with Ki-67 and p53 immunostains and patients followed up. Results: High Ki-67 and p53 immunoexpression was significantly associated with larger tumor size, higher tumor grade, axillary lymph node metastasis, higher disease stage at presentation, lymphovascular invasion, early recurrence, shortened disease free survival and worse overall survival. Conclusions: Ki-67 and p53 immunoexpression can be used as a surrogate biomarker along with other clinicopathological characteristics in resource constrained facilities for better prediction of prognosis of breast cancer patients with positive axillary lymph nodes.

The most recent decade was described by a developing awareness about the seriousness of dementia in the field of age-related people. Among the dementias, Alzheimer's assumes a plentiful role as a result of its amazingly high rate and casualty. A few pharmacological procedures have been attempted yet at the same time now, Alzheimer continues being an untreatable malady. The collection of Aβ in the brain is an early poisonous occasion in the pathogenesis of Alzheimer's disease, which is the most widely recognized type of dementia correlated with plaques and tangles within the brain. However, the mechanism of the intraneuronal direction of BACE1 is poorly understood. AD is caused by mutations in one of the genes that encoding APP, presenilins 1 and 2. Most of the mutations in these genes increase Aβ42 production. Numerous receptors are associated with initiating Aβ transport and clearance. Among them, RAGE is an influx transport receptor that binds soluble Aβ and mediates pathophysiological cellular responses. RAGE additionally intervenes the vehicle of plasma Aβ over the blood-brain barrier. LRP-1 functions as a clearance receptor for Aβ at the blood-brain barrier. The regulation of beta-secretase movement is being explored as a potential restorative focus for treating AD.

OBJECTIVE: To compare the survival outcomes associated with clinical and pathological response in pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant chemotherapy (NAC) with FOLFIRINOX (FLX) or gemcitabine/nab-paclitaxel (GNP) followed by curative-intent pancreatectomy. BACKGROUND: Newer multiagent NAC regimens have resulted in improved clinical and pathological responses in PDAC; however, the effects of these responses on survival outcomes remain unknown. METHODS: Clinicopathological and survival data of PDAC patients treated at 7 academic medical centers were analyzed. Primary outcomes were overall survival (OS), local recurrence-free survival (L-RFS), and metastasis-free survival (MFS) associated with biochemical (CA 19–9 decrease ≥50% vs

Pancreatic cancer remains leading cause of cancer-related death in the United States. Patients with familial pancreas cancer, hereditary pancreatitis, known genetic mutations, and syndromes are deemed high risk for the development of pancreas cancer. Guidelines exist to help facilitate early diagnosis and treatment and these will be reviewed. Pancreatic cancer remains a leading cause of cancer-related death in the United States. Patients with familial pancreatic cancer, hereditary pancreatitis, known genetic mutations, and syndromes are deemed high risk for the development of pancreas cancer. Guidelines have been made to help facilitate early diagnosis and treatment for these patients and these will be reviewed. The exact timing of initial screening depends not only on the individual risk factors but consists of endoscopic ultrasound and magnetic resonance cholangiopancreatography. The frequency of screening depends largely on the findings of initial imaging and the patient's clinical status. We suggest that providers make themselves knowledgeable of current screening recommendations and appropriately apply them. Further critical evaluation of ongoing research is necessary to amend these recommendations as more data and genetic testing becomes available.

Differences in clinical staging and survival among pancreatic head, body, and tail cancers are not well defined. We aim to identify the prognostic relevance of primary tumor location in patients undergoing treatment for pancreatic ductal adenocarcinoma (PDAC).The National Cancer Database was used to identify patients with PDAC from 1998 to 2011 (n = 175,556). Patients were categorized by primary tumor site into head (67.5%, n = 118,343), body (15.5%, n = 27,218), and tail (17.0%, n = 29,885) groups. Univariate and Cox regression analyses were used to determine covariates associated with overall survival (OS).Patients with head PDAC presented with earlier stage disease (39.2% Stage I/II versus 19.7% versus 16.0%, P 0.001) and underwent resection more often (27.9% versus 10.7% versus 17.0%, P 0.001) than those with body or tail tumors. Of surgically resected PDAC, those localized to the head had advanced pathologic stage (84.8% stage II/III versus 66.6% versus 65.6%, P 0.001), higher nodal positivity (64.9% versus 45.8% versus 45%, P 0.001), and worse tumor grade (35.9% poorly differentiated versus 29.5% versus 27.8%, P 0.001). Despite increased utilization of adjuvant therapies (54.4% versus 45.6% versus 42.0%, P 0.001), patients with head PDAC had inferior OS compared with those with body and tail tumors (P 0.001).When examining patients with PDAC undergoing resection, tumor localization to the head is associated with improved resectability because they present earlier. Of resected PDACs, however, those localized to the head have worse OS compared with body and tail tumors. This discrepancy may represent a combination of lead time and selection biases and biologic differences between tumor sites.

Significance Measles vaccine is a highly effective healthcare intervention, but getting vaccine to those in need remains a major problem. Complicating the issue, high-burden countries typically have low-quality infrastructure, severely limiting the number of infections detected and therefore limiting our understanding of local epidemiology. Here we show that statistical disease models can be fitted to sparse case data from Pakistan using a fast linear regression approach. This method yields estimates of the effects of past interventions, the seasonal likelihood of measles transmission, and the magnitude of future outbreaks under different intervention policies. We use these models to understand in general when and where vaccine should be distributed, and these results were used to inform Pakistan’s 2018 vaccination campaign planning., Measles remains a major contributor to preventable child mortality, and bridging gaps in measles immunity is a fundamental challenge to global health. In high-burden settings, mass vaccination campaigns are conducted to increase access to vaccine and address this issue. Ensuring that campaigns are optimally effective is a crucial step toward measles elimination; however, the relationship between campaign impact and disease dynamics is poorly understood. Here, we study measles in Pakistan, and we demonstrate that campaign timing can be tuned to optimally interact with local transmission seasonality and recent incidence history. We develop a mechanistic modeling approach to optimize timing in general high-burden settings, and we find that in Pakistan, hundreds of thousands of infections can be averted with no change in campaign cost.

Traditionally, intraductal papillary mucinous neoplasms (IPMNs) of the pancreas with "high risk stigmata" (HRS) or "worrisome features" (WF) are referred for resection. We aim to assess if IPMN location is predictive of harboring either high grade dysplasia (HGD) or invasive cancer (IC).Patients undergoing resection for IPMN from seven institutions between 2000 and 2015 (n = 275) were analyzed. HRS and WF were defined by the 2012 Fukuoka international consensus guidelines.168 (61%) patients had head/uncinate cysts, while 107 (39%) had neck/body/tail cysts. No differences were noted between groups with regard to age, duct type, cyst size, or presence of at least one WF. Patients with cysts in the head/uncinate were more often male (55% vs. 40%), had at least one HRS (24% vs. 11%), and more often harbored HGD or IC(49% vs. 27%)[all p 0.05]. On multivariate analysis, only cyst location in the head/uncinate remained associated with presence of HGD or IC(odds ratio 4.76, p = 0.02).Cyst location is predictive of HGD or IC in patients with IPMNs. Head/uncinated cysts are more likely to harbor malignancy compared to those of the neck/body/tail. Additional studies are needed to confirm these findings, however, cyst location should be considered part of the decision making process for surveillance vs. resection for IPMNs.

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children’s hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.

Primary tumor location has been shown to be prognostic of overall survival (OS) in patients with both locally advanced and metastatic colorectal cancer. The impact of sidedness on prognosis has not been evaluated in the setting of peritoneal-only metastases treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). A retrospective review of prospectively maintained databases of patients with peritoneal surface malignancy undergoing CRS/HIPEC from three high-volume centers was performed. A total of 115 patients with metastatic colon cancer to the peritoneum who underwent CRS/HIPEC with mitomycin C were identified. Fifty-one patients (45%) had left-sided primary tumors, and 64 (55%) had right-sided primary tumors. Patients with right-sided tumors were more likely to be older (median age 56 vs. 49 years, p = 0.007) and to have signet ring cell histology (17% vs. 4%, p = 0.026). Patients with right-sided tumors had median disease-free survival (DFS) and OS of 14 months (95% confidence interval [CI] 10.5–17.5) and 36 months (95% CI 27.4–44.6), respectively, versus 16 months (95% CI 11.0–21.0) and 69 months (95% CI 24.3–113.7) for those patients with left-sided tumors. On multivariate analysis, primary tumor side was an independent predictor of both DFS and OS. In this study, there was a dramatic, clinically significant difference in OS between patients with right- and left-sided tumors, and primary tumor side was an independent predictor of DFS and OS. Primary tumor side should be considered in patient selection for CRS with or without HIPEC.

Context and Aim: Glycemic imbalance, especially hypoglycemia, is one of the greatest risks for patients with type 2 diabetes mellitus (T2DM) during Ramadan fasting. This paper outlines the efficacy and safety of gliclazide extended release (XR) in Indian patients with T2DM enrolled in the global DIA-RAMADAN study. Methods and Material: Adults (aged ≥18 years) with T2DM who chose to fast during Ramadan and received a gliclazide-based regimen once daily for 90 days before Ramadan were included in the study. Baseline and end-of-study visits were conducted 6–8 weeks before and 4–6 weeks after Ramadan, respectively. Primary outcome was the incidence of ≥1 symptomatic hypoglycemic event (HE). Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were secondary outcomes. Results: Among 246 Indian patients enrolled in the study, most (78.9%, n=194) were at moderate/low risk as per the International Diabetes Federation and Diabetes and Ramadan guidelines. Most patients (69.1%) received gliclazide XR as monotherapy, and the rest received gliclazide XR with metformin or other antidiabetic therapy. Significant reductions in HbA1c (−0.5±0.8%, P

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by irreversible and progressive neurodegeneration. Cholinergic dysfunction has been reported in AD, and several cholinesterase inhibitors, including natural compounds and synthetic analogs, have been developed to treat the disease. However, there is currently no treatment for AD, as most drug-like compounds have failed in clinical trials.&nbsp, Acetylcholinesterase (AChE) is the target of most drugs used commercially to treat AD. This work focused on screening natural compounds obtained from the ZINC database (224, 205 compounds) against AChE to identify those possibly capable of enabling the management of AD. Indirubin and dehydroevodiamine were the best potential AChE inhibitors with free binding energies of −10.03 and −9.00 kcal/mol, respectively. The key residue (His447) of the active site of AChE was found to participate in complex interactions with these two molecules. Six H-bonds were involved in the ‘indirubin–AChE’ interaction and three H-bonds in the ‘dehydroevodiamine–AChE’ interaction. These compounds were predicted to cross the blood–brain barrier (BBB) and to exhibit high levels of intestinal absorption. Furthermore, ‘indirubin–AChE’ and ‘dehydroevodiamine–AChE’ complexes were found to be stable, as determined by root mean square deviation (RMSD) during a 50 ns molecular dynamics simulation study. Based on the free binding energies and stabilities obtained by simulation studies, we recommend that experimental studies be undertaken on indirubin and dehydroevodiamine with a view towards their potential use as treatments for AD.

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c ), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n=84) with adults (n=195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p=0.002), pylorus preservation (93% versus 67%; p

The mitochondrial voltage-gated potassium channel, Kv1.3, has been emerged as an attractive oncologic target but its function in pancreas cancer (PDAC) is unknown. In this study we evaluated tissue expression of Kv1.3 in resected PDAC from 55 patients and tumor inhibition in orthotopic mouse models using the recently developed Kv1.3 inhibitors PCARBTP and PAPTP. Immunohistochemistry of 55 human PDAC specimens showed that all tumors expressed Kv1.3 with 60% of tumor specimens having high Kv1.3 expression. In pancreas tumor models (Pan02 cells injected into C57BL/6 mice), PCARBTP and PAPTP treatment resulted in tumor reductions of 87% and 70%, respectively. When combined with gemcitabine/abraxane, this increased to 95% and 80% without resultant organ toxicity. In vivo models indicated PCARBTP-mediated cell death occurred through the p38-MAPK pathway. In vitro-generated resistant clones to PCARBTP escaped cell death through upregulation of the anti-oxidant system as determined using SWATH-MS analysis. These data show Kv1.3 is highly expressed in resected human PDAC and the use of novel mitochondrial Kv1.3 inhibitors combined with cytotoxic chemotherapies might be novel, effective treatment for PDAC.

Alzheimer's Disease (AD) is a chronic neurodegenerative disease. It is clinically characterized by memory loss and intellectual decrease, among other neurological deficits. The etiology of AD is not completely understood but includes amyloid plaques and intracellular helical filaments as well as neurofibrillary tangles with hyperphosphorylated tau protein. AD is also associated with alterations in amyloid processing genes, such as PSEN1 or PSEN2 and APP. The modulation of the immune system, cholesterol metabolism, and synaptic vesicle endocytosis have all been shown to remediate AD. In this review, enzymes such as AChE, BuChE, β-secretase, γ-secretase, MAO, and RAGE are discussed as potential targets for AD treatment. The aim of this review was to address the molecular mechanisms as well as various genetic factors in AD etiology. The use of natural compounds against these targets might be beneficial for the management of AD.