Rescue from complications after pancreaticoduodenectomies at a low-volume Caribbean center:Value of tailored peri-pancreatectomy protocols

BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tailored protocols were instituted at our low volume facility in the year 2013.AIM To document the rate of rescue from post-PD complications with tailored protocols in place as a measure of quality.METHODS A retrospective audit was performed to collect data from patients who experienced major post-PD complications at a low volume pancreatic surgery unit in Trinidad and Tobago between January 1,2013 and June 30,2023.Stan-dardized definitions from the International Study Group of Pancreatic Surgery were used to define post-PD complications,and the modified Clavien-Dindo classification was used to classify post-PD complications.RESULTS Over the study period,113 patients at a mean age of 57.5 years(standard deviation[SD]±9.23;range:30-90;median:56)underwent PDs at this facility.Major complications were recorded in 33(29.2%)patients at a mean age of 53.8 years(SD:±7.9).Twenty-nine(87.9%)patients who experienced major morbidity were salvaged after aggre-ssive treatment of their complication.Four(3.5%)died from bleeding pseudoaneurysm(1),septic shock secondary to a bile leak(1),anastomotic leak(1),and myocardial infarction(1).There was a significantly greater salvage rate in patients with American Society of Anesthesiologists scores≤2(93.3%vs 25%;P=0.0024).CONCLUSION This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring PD.Despite low volumes at our facility,we demonstrated that 87.9%of patients were rescued from major complications.We attributed this to several factors including development of rescue protocols,the competence of the pancreatic surgery teams and continuous,and adaptive learning by the entire institution,cul-minating in the development of tailored peri-pancreatectomy protocols.

Memory Training and Task Specificity in 90-99-Year-Old Seniors with Mild Cognitive Impairment

Managing memory deficits is a central problem among older adults with mild cognitive impairment (MCI). This study examined the effects of memory training on memory performance in an understudied “oldest-old” population ranging in age from 90 to 99 years. Eighteen mild to moderately cognitive-impaired older seniors, 90 years and older were recruited from memory clinics established in senior living communities. Treatment sessions took place, on average, twice weekly, for 55 minutes. Memory intervention included nineteen computer-based exercises customized to focus on memory loss. The specificity of memory training was very clear;memory training produced significant effects (F(3,51) = 2.81, p = 0.05) on memory performance, especially after 6 months of training, while other outcome measures showed no effects as predicted. Based on the results, it can be concluded that interventions targeting cognition and memory in the oldest-old MCI population can significantly improve memory function and reduce cognitive deficits.

A Multi-Center International Survey Related to the Nutritional Support after Hematopoietic Stem Cell Transplantation Endorsed by the ASIA Pacific Blood and Marrow Transplantation (APBMT)

Background: The nutritional support after hematopoietic stem cell transplantation (HSCT) has not been well established due to the scarcity of clinical trials. To conduct international clinical trials in Asia, we performed the questionnaire survey to investigate the current standard of nutritional support after HSCT. Method: We sent the questionnaire to the physicians nominated by the Asia Pacific Blood and Marrow Transplantation (APBMT) members of each country/ region. Result: We received 15 responses from 7 different countries/regions. The target calorie amount is 1.0 - 1.3 × basal energy expenditure (BEE) in 11 institutes when partial parenteral nutrition is used. When total parenteral nutrition (TPN) is used, the target calorie amount is 1.0 - 1.3 × BEE in 9 institutes and 1.3 - 1.5 × BEE in 4 institutes. Lipid emulsion is routinely used in 12 institutes. Multivitamins and trace elements are routinely added to TPN used in most institutes. It is still uncommon to use the immunonutrition. Blood glucose levels are routinely monitored in all institutes, but the target range varies (<110 in 2 institutes, <150 in 4 institutes, and <200 in 8 institutes). Conclusions: Basic nutritional support is similar in participating institutes. However, the target glucose level varies and the use of immunonutrition is rather rare. These points can be the theme of future clinical trials.

Nine Months of Memory Training Increases Cognistat Measured Memory in 79 - 89 Year-Old Mild Cognitively Impaired Individuals

The effects of a memory training paradigm on performance across multiple cognitive domains, measured via the Cognistat, in 70 - 89 year-old individuals with mild cognitive impairment (MCI), were examined. Memory training sessions were conducted on average twice weekly, for 55 minutes each session, for 9 months. Across the testing period, Cognistat-measured memory increased relative to performance in other cognitive domains. Additionally, performance on non-memory measures remained stable or declined. Thus, memory training in older adult, MCI individuals may result in improved memory, but not in improvement in other, non-memory, cognitive domains. Results replicate previous work examining “oldest-old” individuals ranging in age from 90 to 99 years old at the time of study start.

A Brief Report Investigating Subjective and Objective Memory Pre- and Post-Memory Training in 70- to 96-Year-Old Individuals with Mild Memory Deficit

Subjective memory impairment is a major complaint among older adults;however, research is conflicting regarding the relationship between subjective memory impairment and objectively measured memory loss. Here, individuals with mild memory impairment completed the memory subscale of the Cognistat as a measure of objective memory, and the Memory Complaint Questionnaire (MCQ) as a measure of subjective memory, prior to and following a 3-month memory training program. Results revealed that individuals with more, compared with fewer, memory complaints performed worse on the Cognistat. Additionally, increased Cognistat performance fol-lowing the memory training procedure was associated with decreased MCQ measured complaints. There was suggestive evidence that the memory training procedure improved memory, and thus future research is warranted. These findings imply that older, memory-impaired, adults, despite their memory impairment, are indeed able to judge, and may be accurately concerned with, the extent of their own memory loss. It should be noted that serious statistical limitations here indicate the need for replication to confirm the validity of the findings.

Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated.Objectives: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one another.Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022.Results: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

Cyclin-dependent kinase 1 （Cdkl）/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 （also known as Cdk5rap3 and LZAP） potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. （2007） found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We re- port here the identification of C53 protein as a novel regulator of Cdkl activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 （Chkl and Chk2） is partially inhibited by C53 overexpression. Intriguingly, we found that C53 inter- acts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdkl activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chkl, C53 promotes Cdkl activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

The clinical value, principle, and basic practical technique of mindfulness intervention

正念干预是基于佛教修行的冥想,结合当代心理学理论和方法所发展的一种心理疗法。近年来的实证研究表明正念干预在降低抑郁复发,缓解抑郁、焦虑症状,减少物质滥用,减轻疼痛,血压管理,提高免疫力,改善睡眠等方面的应用均产生了良好的效果。当前,正念疗法在欧美心理治疗界中已成为心理治疗的主流。近几年我国心理学界和心理治疗领域也开始对正念治疗进行介绍,但在临床精神健康领域却缺乏相关的实践和研究。本文将对正念的概念,干预的基本机制,临床实践中的基本技能和指导原则简要介绍。

Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis

To investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score).METHODSWe reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed.RESULTSWe identified 99 patients (53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity (62%), consideration of medication change (10%), assessment of medication efficacy (14%), and cancer screening (14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was “moderate-substantial” agreement between the two reviewers in assessing rectal Mayo scores (kappa = 0.54, 95%CI: 0.41-0.68).CONCLUSIONEndoscopic disease severity (Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.

Continuing challenges in the diagnosis and management of obscure gastrointestinal bleeding

The diagnosis and management of obscure gastrointestinal bleeding(OGIB) have changed dramatically since the introduction of video capsule endoscopy(VCE) followed by deep enteroscopy and other imaging technologies in the last decade. Significant advances have been made, yet there remains room for improvement in our diagnostic yield and treatment capabilities for recurrent OGIB. In this review, we will summarize the latest technologies for the diagnosis of OGIB, limitations of VCE, technological enhancement in VCE, and different management options for OGIB.

Anal squamous cell carcinoma: An evolution in disease and management

Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.

Endoscopy and polyps-diagnostic and therapeutic advances in management

Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.

Viral infections and cell cycle G2/M regulation

Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well- characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

Prosthetic joint infections-a clinico-microbiological perspective: Review article

Prosthetic joint infections(PJIs),although not very common,currently pose a very significant threat since they are associated with severe complications,high morbidity rates and substantial costs.PJIs are most commonly caused by Staphylococcus aureus and coagulase-negative staphylococci.The diagnosis of implant-associated infections is very challenging since no single routinely used laboratory or clinical test has been shown to demonstrate adequate results with respect to sensitivity,specificity and accuracy.In most cases,a sum of clinical signs and symptoms,histopathology,blood tests,radiography,bone scans and microbiological testing is considered to arrive at an accurate diagnosis.Treatment of PJIs is also very difficult since most of the infections are caused by biofilm-producing microorganisms which are significantly more resistant to the hosts natural defense mechanisms and antibiotic treatment.For successful management,a combination of both antibiotic and surgical treatment is most often required,and early diagnosis is of the utmost importance.Thus,a multidisciplinary approach is potentially the best option in dealing with PJI,and should include the involvement of microbiologists,orthopedic specialists,clinicians,pathologists and radiologists in order to improve decision-making processes and ensure overall success.The following review aims at briefly outlining the microbiology,diagnostic and treatment options,and preventive measures associated with such infections.

Surgical approach for hepatitis C virus-related hepatocellular carcinoma

Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma(HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC,adequate management of co-existing infection with hepatitis C virus(HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection,perioperative anti-viral treatment is recommended,since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease,the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy,new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.

Potential role of human papilloma virus in the pathogenesis of gastric cancer

AIM: To demonstrate the presence and biological activity of human papilloma virus (HPV) in gastric cancer (GAC) tissues.

Management of hypertensive crises in the elderly

Hypertensive crises are elevations of blood pressure higher than 180/120 mmHg. These can be urgent or emergent, depending on the presence of end organ damage. The clinical presentation of hypertensive crises is quite variable in elderly patients, and clinicians must be suspicious of non-specific symptoms. Managing hypertensive crises in elderly patients needs meticulous knowledge of the pathophysiological changes in them, pharmacological options, pharmacokinetics of the medications used, their side effects, and their interactions with other medications. Clevidipine, nicardipine, labetalol, esmolol, and fenoldopam are among the preferred choices in the elderly due to their efficacy and tolerability. Nitroprusside, hydralazine, and nifedipine should be avoided, unless there are no other options available, due to the high risk of complications and unpredictable responses.

Hepatitis B infection among adults in the philippines:A national seroprevalence study

AIM:To determine the prevalence of hepatitis B surface antigen(HBsAg)seropositivity among adult Filipinos.METHODS:Testing for HBsAg was performed on serum samples from persons aged ≥ 20 years old who participated in the National Nutrition and Health Survey(NNHeS)conducted in 2003.Information on age,sex,marital status,educational attainment,employment status,and income were collected.For this study,marital status was classified as never married or otherwise(i.e.,married,divorced,separated,widowed);educational attainment was classified as high school graduate or below or at least some tertiary education;and employment status was classified as currently employed or currently unemployed.Annual income was divided into 4 quartiles in Philippine pesos(PhP):Q1,≤ PhP 53064;Q2,PhP 53065-92192;Q3,PhP 92193-173387;and Q4,≥ PhP 173388.Prevalence estimates were weighted so that they represented the general population.Social and demographic factors were correlated with HBsAg seropositivity.Multivariate analysis was used to determine independent predictors of HBsAg seropositivity.RESULTS:A total of 2150 randomly selected adults,20 years and over,out of the 4753 adult participants of NNHeS were tested for HBsAg.The HBsAg seroprevalence was 16.7%(95%CI:14.3%-19.1%),which corresponded to an estimated 7278968 persons infected with hepatitis B.There was no significant difference between males and females(17.5% vs 16.0%;P = 0.555).This corresponded to an estimated 3721775 men and 3557193 women infected with hepatitis B.The HBsAg seroprevalence peaked at age 20-39 years old,with declining prevalence in the older age groups.The only independent predictor of HBsAg seropositivity was the annual income,with persons in the highest income quartile being less likely to be HBsAg positive(age-adjusted OR = 0.51;95%CI:0.30-0.86)compared to subjects in the lowest income quartile.Sex,marital status,educational attainment,and employment status were not found to be independent predictors of HBsAg seropositivity.CONCLUSION:The high HBsAg seroprevalence among adults in the Philippines classifies the country as hyperendemic for HBV infection and appears unchanged over the last few decades.

Routine colonic endoscopic evaluation following resolution of acute diverticulitis:Is it necessary?

Diverticular disease incidence is increasing up to 65% by age 85 in industrialized nations,low fiber diets,and in younger and obese patients.Twenty-five percent of patients with diverticulosis will develop acute diverticulitis.This imposes a significant burden on healthcare systems,resulting in greater than 300000 admissions per year with an estimated annual cost of $3 billion USD.Abdominal computed tomography(CT) is the diagnostic study of choice,with a sensitivity and specificity greater than 95%.Unfortunately,similar CT findings can be present in colonic neoplasia,especially when perforated or inflamed.This prompted professional societies such as the American Society of Colon Rectal Surgeons to recommend patients undergo routine colonoscopy after an episode of acute diverticulitis to rule out malignancy.Yet,the data supporting routine colonoscopy after acute diverticulitis is sparse and based small cohort studies utilizing outdated technology.While any patient with an indication for a colonoscopy should undergo appropriate endoscopic evaluation,in the era of widespread use of high-resolution computed tomography,routine colonic endoscopic evaluation following resolution of acute uncomplicated diverticulitis poses additional costs,comes with inherent risks,and may require further study.In this manuscript,we review the current data related to this recommendation.

Pimavanserin for the treatment of psychosis in Alzheimer’s disease: A literature review

BACKGROUND Alzheimer’s disease(AD)is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed(AD+vascular)dementias.Approximately 25%-50%of individuals with AD develop psychosis sometime during their illness.The presence of psychosis in AD worsens outcomes.Currently there are no United States Food and Drug Administration(FDA)approved medications for the treatment of psychosis in AD.Pimavanserin,a novel atypical antipsychotic medication,was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson disease psychosis and is currently in clinical trials for the treatment of psychosis in AD.AIM To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD.METHODS A literature review of clinical studies of pimavanserin treatment for psychosis in individuals with AD was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.Trials were identified by systematically searching PubMed,MEDLINE,EMBASE,Cochrane Central Register of Controlled Trials,Web of Science,and Scopus through October 2019.The 5-point Jadad scoring system was used to assess the methodologic quality of the randomized placebo-controlled trials.RESULTS A total of 499 citations were retrieved and pooled in EndNote and de-duplicated to 258 citations.This set was uploaded to Covidence for screening.Two separate screeners(Srinivasan S and Tampi RR)evaluated the titles,abstracts,and full text of eligible articles.Of the identified 258 abstracts,98 articles underwent full text review and 2 publications from 1 randomized controlled trial(RCT)were included in the final analysis.The quality of evidence was assessed to be of good methodologic quality,scoring 4 out of 5 using the 5-point Jadad questionnaire with the Jadad Scoring calculation.This systematic review found only one RCT that evaluated the use of pimavanserin for the treatment of psychosis among individuals with AD.This phase 2 trial resulted in two publications,the second of which was a subgroup analysis from the original study.The evidence from these two publications showed that pimavanserin improves psychotic symptoms among individuals with AD when compared to placebo at week 6.CONCLUSION Pimavanserin may be a pharmacologic consideration for the treatment for psychosis in AD.Additional RCTs are needed to assess the evidence of effectiveness before pimavanserin is considered a standard treatment.