Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

Can Computerized Simulation be Used to Assess Surgical Proficiency in Laparoscopic Colorectal Surgeries? A Systematic Review.

INTRODUCTION: Computerized simulation (CS) of surgery in virtual reality (VR), augmented reality (AR) and mixed reality (MR) settings are used to teach foundational skills, but its applicability in advanced training is to be determined. This review aims to summarize the types of CS available for laparoscopic colorectal surgery (CRS) and its utility in assessment of proficiency. METHODS: A systematic review of CS in laparoscopic CRS was done on PubMed, Embase, Scopus and Cochrane Library databases. RESULTS: Eleven relevant observational studies were identified. The most common procedure simulated was laparoscopic colectomy. Assessment using performance metrics measured by the simulator such as path length moved by laparoscopic tools, procedure time and number of discrete movements had the most consistent differentiating ability between expert and non-expert cohorts. Surgeons fared similarly in proficiency scores in assessment with CS compared to assessment with traditional cadaveric or porcine models. CONCLUSION: CS of laparoscopic CRS may be used in assessment of proficiency using performance metrics measuring economy of movement. CS may be a viable assessment tool in advanced surgical training, but further studies should assess utility of incorporating it as a formal assessment tool in training programs.

Exploring the learning curve in minimally invasive esophagectomy: a systematic review.

Minimally invasive esophagectomy (MIE) has been shown to be superior to open esophagectomy with reduced morbidity, mortality, and comparable lymph node (LN) harvest. However, MIE is technically challenging. This study aims to perform a pooled analysis on the number of cases required to surmount the learning curve (LC), i.e. NLC in MIE. PubMed, Embase, Scopus, and the Cochrane Library were systematically searched for articles from inception to June 2022. Inclusion criteria were articles that reported LC in video-assisted MIE (VAMIE) and/or robot-assisted MIE (RAMIE). Poisson means (95% confidence interval [CI]) was used to determine NLC. Negative binomial regression was used for comparative analysis. There were 41 articles with 45 data sets (n = 7755 patients). The majority of tumors were located in the lower esophagus or gastroesophageal junction (66.7%, n = 3962/5939). The majority of data sets on VAMIE (n = 16/26, 61.5%) used arbitrary analysis, while the majority of data sets (n = 14/19, 73.7%) on RAMIE used cumulative sum control chart analysis. The most common outcomes reported were overall operating time (n = 30/45) and anastomotic leak (n = 28/45). Twenty-four data sets (53.3%) reported on LN harvest. The overall NLC was 34.6 (95% CI: 30.4-39.2), 68.5 (95% CI: 64.9-72.4), 27.5 (95% CI: 24.3-30.9), and 35.9 (95% CI: 32.1-40.2) for hybrid VAMIE, total VAMIE, hybrid RAMIE, and total RAMIE, respectively. NLC was significantly lower for total RAMIE compared to total VAMIE (incidence rate ratio: 0.52, P = 0.032). Studies reporting NLC in MIE are heterogeneous. Further studies should clearly define prior surgical experiences and assess long-term oncological outcomes using non-arbitrary analysis.

Learning curve of laparoscopic and robotic total gastrectomy: A systematic review and meta-analysis.

PURPOSE: Minimally-invasive total gastrectomy (MITG) is associated with lower morbidity in comparison to open total gastrectomy but requires a learning curve (LC). We aimed to perform a pooled analysis of the number of cases required to surmount the LC (NLC) in MITG. METHODS: A systematic review of PubMed, Embase, Scopus and the Cochrane Library from inception until August 2022 was performed for studies reporting the LC in laparoscopic total gastrectomy (LTG) and/or robotic total gastrectomy (RTG). Poisson mean (95% confidence interval [CI]) was used to determine the NLC. Negative binomial regression was performed as a comparative analysis. RESULTS: There were 12 articles with 18 data sets: 12 data sets (n = 1202 patients) on LTG and 6 data sets (n = 318 patients) on RTG. The majority of studies were conducted in East Asia (94.4%). The majority of the data sets (n = 12/18, 66.7%) used non-arbitrary analyses. The NLC was significantly smaller in RTG in comparison to LTG [RTG 20.5 (95% CI 17.0-24.5); LTG 43.9 (95% CI 40.2-47.8); incidence rate ratio 0.47, p < 0.001]. The NLC was comparable between totally-laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG) [LATG 39.0 (95% CI 30.8-48.7); TLTG 36.0 (95% CI 30.4-42.4)]. CONCLUSIONS: The LC for RTG was significantly shorter for LTG. However existing studies are heterogeneous.

Surveillance to achieve malaria elimination in eastern Myanmar: a 7-year observational study.

BACKGROUND: The collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance. METHODS: This retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time. RESULTS: In the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard. CONCLUSIONS: Surveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.

Does technology-enhanced communication improve Helicobacter pylori eradication outcomes?-A meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) is a highly prevalent organism that can induce an inflammatory state in the upper gastrointestinal tract and lead to complications such as peptic ulcer and gastric cancer. The treatment regime is complicated, and mild-to-moderate adverse effects are common, making patient compliance a key determinant of successful eradication. One attractive strategy is to leverage on technology-enhanced communication (TEC) strategies. However, the current data on the efficacy of TEC modalities in improving H. pylori eradication are limited. This is the first meta-analysis evaluating its effectiveness to the best of our knowledge. Thus, it is essential to evaluate the current body of evidence to learn the impact of TEC initiatives. METHODS: A literature search was done on PubMed, World of Science, and Embase. A total of 9 studies variably reported on compliance rate, eradication rate, adverse effect rate, symptom relief, patient satisfaction, treatment cost, patient disease awareness, and follow-up rates. RESULTS: This meta-analysis showed that TEC initiatives significantly improve patient compliance (OR 4.52, 95% CI 2.09 - 9.77, p < .01) and eradication rate (OR 1.98, 95% CI 1.34 - 2.93, p < .01) but not adverse effect rate (OR 0.65, 95% CI [0.27 - 1.57], p = .34). Due to the small number of studies and population sample, patient satisfaction, symptom relief, treatment costs, disease awareness, and follow-up rates were assessed qualitatively. CONCLUSION: TEC initiatives effectively improve compliance to the H. pylori eradication regime and increase the eradication rate.

Longitudinal trends in malaria testing rates in the face of elimination in eastern Myanmar: a 7-year observational study.

BACKGROUND: Providing at-risk communities with uninterrupted access to early diagnosis and treatment is a key component in reducing malaria transmission and achieving elimination. As programmes approach malaria elimination targets it is critical that each case is tested and treated early, which may present a challenge when the burden of malaria is reduced. In this paper we investigate whether malaria testing rates decline over time and assess the impacts of integrating malaria and non-malaria services on testing rates in the malaria elimination task force (METF) programme in the Kayin state of Myanmar. METHODS: A retrospective analysis was conducted using weekly collected data on testing rates from a network of more than 1200 malaria posts during the period from 2014 to 2020. To determine whether monthly testing rates changed over the years of programme operations, and whether integrating malaria and non-malaria services impacted these testing rates, we fitted negative binomial mixed-effects regression models to aggregate monthly data, accounting for malaria seasonal variation. RESULTS: In the first year of malaria post operation, testing rates declined, correlating with a decline in attendance by people from outside the malaria post catchment area, but then remained fairly constant (the Rate Ratio (RR) for 2nd versus 1st year open ranged from 0.68 to 0.84 across the four townships included in the analysis, the RR for 3rd to 6th year versus 1st year open were similar, ranging from 0.59-0.78). The implementation of a training programme, which was intended to expand the role of the malaria post workers, had minimal impact on testing rates up to 24 months after training was delivered (RR for integrated versus malaria-only services ranged from 1.00 to 1.07 across METF townships). CONCLUSION: Despite the decline in malaria incidence from 2014 to 2020, there has been no decline in the malaria testing rate in the METF programme after the establishment of the complete malaria post network in 2016. While the integration of malaria posts with other health services provides benefits to the population, our evaluation questions the necessity of integrated services in maintaining malaria testing rates in areas approaching elimination of malaria.

Automating the Generation of Antimicrobial Resistance Surveillance Reports: Proof-of-Concept Study Involving Seven Hospitals in Seven Countries.

BACKGROUND: Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel. OBJECTIVE: This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly. METHODS: An offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access example data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People's Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam. RESULTS: We developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from https://www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository. CONCLUSIONS: The AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.

Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme.

BACKGROUND: Potentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrupts transmission. We examined the effects of a scaled-up programme of this strategy in four townships of eastern Myanmar on the incidence of P falciparum malaria. METHODS: The programme was implemented in the four townships of Myawaddy, Kawkareik, Hlaingbwe, and Hpapun in Kayin state, Myanmar. Increased access to early diagnosis and treatment of malaria was provided to all villages through community-based malaria posts equipped with rapid diagnostic tests, and treatment with artemether-lumefantrine plus single low-dose primaquine. Villages were identified as malarial hotspots (operationally defined as >40% malaria, of which 20% was P falciparum) with surveys using ultrasensitive quantitative PCR either randomly or targeted at villages where the incidence of clinical cases of P falciparum malaria remained high (ie, >100 cases per 1000 individuals per year) despite a functioning malaria post. During each survey, a 2 mL sample of venous blood was obtained from randomly selected adults. Hotspots received targeted mass drug administration with dihydroartemisinin-piperaquine plus single-dose primaquine once per month for 3 consecutive months in addition to the malaria posts. The main outcome was the change in village incidence of clinical P falciparum malaria, quantified using a multivariate, generalised, additive multilevel model. Malaria prevalence was measured in the hotspots 12 months after mass drug administration. FINDINGS: Between May 1, 2014, and April 30, 2017, 1222 malarial posts were opened, providing early diagnosis and treatment to an estimated 365 000 individuals. Incidence of P falciparum malaria decreased by 60 to 98% in the four townships. 272 prevalence surveys were undertaken and 69 hotspot villages were identified. By April 2017, 50 hotspots were treated with mass drug administration. Hotspot villages had a three times higher incidence of P falciparum at malarial posts than neighbouring villages (adjusted incidence rate ratio [IRR] 2·7, 95% CI 1·8-4·4). Early diagnosis and treatment was associated with a significant decrease in P falciparum incidence in hotspots (IRR 0·82, 95% CI 0·76-0·88 per quarter) and in other villages (0·75, 0·73-0·78 per quarter). Mass drug administration was associated with a five-times decrease in P falciparum incidence within hotspot villages (IRR 0·19, 95% CI 0·13-0·26). By April, 2017, 965 villages (79%) of 1222 corresponding to 104 village tracts were free from P falciparum malaria for at least 6 months. The prevalence of wild-type genotype for K13 molecular markers of artemisinin resistance was stable over the three years (39%; 249/631). INTERPRETATION: Providing early diagnosis and effective treatment substantially decreased village-level incidence of artemisinin-resistant P falciparum malaria in hard-to-reach, politically sensitive regions of eastern Myanmar. Targeted mass drug administration significantly reduced malaria incidence in hotspots. If these activities could proceed in all contiguous endemic areas in addition to standard control programmes already implemented, there is a possibility of subnational elimination of P falciparum. FUNDING: The Bill & Melinda Gates Foundation, the Regional Artemisinin Initiative (Global Fund against AIDS, Tuberculosis and Malaria), and the Wellcome Trust.

A rare case of bipartite combined tumour of the oesophagus.

BACKGROUND: Bipartite combined oesophageal tumours are an exceedingly rare entity and much less is known about the natural history of these tumours following curative surgery. The authors present a case of a bipartite combined oesophageal tumour comprising of sarcomatoid carcinoma and small cell carcinoma with early postoperative recurrence. CASE PRESENTATION: A 63-year-old Chinese male with a smoking history presents with hemoptysis on a background of dysphagia and odynophagia for 1 month. An endoscopic evaluation found an exophytic oesophageal tumour with contact bleeding for which biopsy of this lesion returned as a malignant high-grade tumour where immunohistochemistry staining was unable to establish the lineage of the tumour. Differential diagnoses include sarcomatoid carcinoma and malignant undifferentiated sarcoma. With the provisional diagnosis of a high-grade oesopheageal sarcoma, the patient underwent minimally invasive McKeown's oesophagectomy. Final histological assessment was pT1bN0 with two histological types of malignancy within a single tumour-70% poorly differentiated spindle cell squamous carcinoma and small cell carcinoma. He was planned for adjuvant chemotherapy in view of the small cell carcinoma component after the resolution of the postoperative infective collections. A computed tomographic scan performed 4 months postoperatively demonstrated metastasis to the lung, pleura, thoracic nodes and liver. Biopsy of the largest lung nodule confirmed small cell neuroendocrine carcinoma with features similar to the small cell carcinoma component in the prior oesophagectomy specimen. He was thereafter initiated on palliative chemotherapy aimed at three weekly carboplatin and etoposide aimed at a total of 4 cycles with peglasta support. Etoposide was stopped during the first cycle due to asymptomatic bradycardia. The regime was then converted to carboplatin with irinotecan for 5 cycles. Repeat computed tomographic scan performed 3 weeks after the completion of chemotherapy showed a complete response of lung and liver metastasis and no evidence of local recurrence or distant metastasis. CONCLUSION: The management of bipartite combined oesophageal tumours should be guided by its more aggressive component. Bipartite combined oesophageal tumours with a small cell carcinoma component are believed to demonstrate aggressive tumour biology likened to that of primary oesophageal small cell carcinoma. Preoperative confirmation of a combined tumour may be challenging, and biopsy results may only yield one of the two components. The more aggressive component is usually a small cell carcinoma, for which the mainstay of therapy is platinum-based chemotherapy rather than surgery.

Poor response to artesunate treatment in two patients with severe malaria on the Thai-Myanmar border.

BACKGROUND: Malaria has declined dramatically along the Thai-Myanmar border in recent years due to malaria control and elimination programmes. However, at the same time, artemisinin resistance has spread, raising concerns about the efficacy of parenteral artesunate for the treatment of severe malaria. CASE PRESENTATION: In November 2015 and April 2017, two patients were treated for severe malaria with parenteral artesunate. Quinine was added within 24 h due to an initial poor response to treatment. The first patient died within 24 h of starting treatment and the second did not clear his peripheral parasitaemia until 11 days later. Genotyping revealed artemisinin resistance Kelch-13 markers. CONCLUSIONS: Reliable efficacy of artesunate for the treatment of severe malaria may no longer be assured in areas where artemisinin resistance has emerged. Empirical addition of parenteral quinine to artesunate for treatment is recommended as a precautionary measure.

The role of early detection and treatment in malaria elimination.

Falciparum malaria persists in hard-to-reach areas or demographic groups that are missed by conventional healthcare systems but could be reached by trained community members in a malaria post (MP). The main focus of a MP is to provide uninterrupted and rapid access to rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) too all inhabitants of a village. RDTs allow trained community members to perform malaria diagnosis accurately and prescribe appropriate treatment, reducing as much as possible any delay between the onset of fever and treatment. Early treatment with ACT and with a low-dose of primaquine prevents further transmission from human to mosquito. A functioning MP represents an essential component of any malaria elimination strategy. Implementing large-scale, high-coverage, community-based early diagnosis and treatment through MPs requires few technological innovations but relies on a very well structured organization able to train, supervise and supply MPs, to monitor activity and to perform strict malaria surveillance.

Is a robotic system really better than the three-dimensional laparoscopic system in terms of suturing performance?: comparison among operators with different levels of experience.

BACKGROUND: High-quality three-dimensional (3D) vision systems are now available for laparoscopic surgery and may improve surgical performance relative to two-dimensional (2D) laparoscopy. It is unclear whether 3D laparoscopy is superior to 3D robotic systems. The effect of surgeon experience on surgical performance with different instruments also remains unclear. This study compared the ability of experienced and inexperienced surgeons to perform a suturing task with 2D laparoscopy, 3D laparoscopy, and a 3D robot. METHODS: The 20 recruited surgeons consisted of experts (≥100 laparoscopic cases, n = 9), surgeons with intermediate experience (20-99 cases, n = 7), and novices (<20 cases, n = 4). All performed a suturing task three times with each instrument. Task failure rates and completion times were measured. RESULTS: All novices failed to complete the task with 2D or 3D laparoscopy, but all completed the task with the robot. The intermediate group failed the task with 2D laparoscopy (23.8% failure rate) more often than with 3D laparoscopy (4.8%) or the robot (0%; P = 0.04). Expert failure rates were low for all instruments. Intermediate group task completion times were similar to 2D laparoscopy (median 312 s; range 229-495 s), 3D laparoscopy (324 s; 170-443 s), and the robot (319 s; 213-433 s) (P = 0.237). The expert times differed significantly (P = 0.01); post hoc analyses showed that their total completion time with 3D laparoscopy (177 s; 126-217 s) was significantly shorter than with 2D laparoscopy (244 s; 155-270 s; P = 0.004). It also tended to be shorter than with the robot (233 s; 187-461 s; P = 0.027). CONCLUSIONS: Novices benefited particularly from the robot. The intermediate group completed the task equally well and equally quickly with 3D laparoscopy and the robot. The experts completed the task equally well regardless of instrument, but their times were much faster with 3D laparoscopy. Thus, well-trained laparoscopic surgeons may not really benefit from 3D robot systems if 3D laparoscopy is available.

Feasibility of hyperthermic pressurized intraperitoneal aerosol chemotherapy in a porcine model.

BACKGROUND: Peritoneal carcinomatosis is an unmet therapeutic need. Several types of intraperitoneal chemotherapy have been introduced. However, hyperthermic intraperitoneal chemotherapy has limited drug distribution and poor peritoneal penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) does not have the benefits of hyperthermia. We developed a device to apply hyperthermic PIPAC (H-PAC) and evaluated its feasibility in a porcine model. METHODS: The device for H-PAC consisted of a laparoscopic aerosol spray and a heater to create hyperthermic capnoperitoneum. We operated on five pigs for the development of the new device and on another five pigs as a survival model. After a pilot experiment of the survival model (Pig A), a hyperthermic pressurized intraperitoneal aerosol of indocyanine green was administered after insertion of three trocars (Pig B) and laparoscopy-assisted distal gastrectomy (LADG) (Pig C) without chemotherapeutic agents. After that, H-PAC with cisplatin was administered after insertion of three trocars (Pig D) and LADG (Pig E). Autopsies were performed on postoperative day 7. RESULTS: Median operation time was 85 min (80-110 min). Intraperitoneal temperature was constant for 1 h of H-PAC (38.8-40.2 °C). All five pigs were healthy and survived for 7 days. Median weight loss was 0.2 kg. Autopsy tissues of stomach, peritoneum, and jejunum were intact in all five pigs. CONCLUSIONS: H-PAC was feasible and safe in a porcine model.

Eleven-year experience with 3000 cases of laparoscopic gastric cancer surgery in a single institution: analysis of postoperative morbidities and long-term oncologic outcomes.

BACKGROUND: The present study summarizes the 11-year laparoscopic gastric cancer surgery experience of a single institution in South Korea and evaluates the current trends of laparoscopic gastric cancer surgery through our experience. METHODS: A total of 3000 minimally invasive gastric cancer surgeries were performed at Seoul National University Bundang Hospital between May 2003 and January 2014. The types of laparoscopic gastrectomy used, surgical techniques, postoperative morbidities, and long-term oncologic outcomes were analyzed. RESULTS: The proportion of challenging procedures such as laparoscopic total gastrectomy and laparoscopic gastrectomy for patients with advanced gastric cancer increased during the study period. The frequency of laparoscopic function-preserving gastrectomy for patients with early-stage cancer also increased. The overall rate of complications was 16.7 %; surgical and systemic complication rates were 11.8 and 6.2 %, respectively. There was one case of postoperative mortality due to delayed bleeding after discharge. Male gender, high BMI, long operating times, combined resection of other organs, and total and proximal gastrectomies were independent predictors of surgical morbidities; however, pathologic T-stage was not a predictable factor. Accumulated experience in laparoscopic surgery decreased the surgical complication rates of total and proximal gastrectomies more than it did in distal gastrectomy over time. The 5-year overall survival rates of patients in advanced stages and those who underwent laparoscopic total gastrectomy were comparable to those reported previously. CONCLUSIONS: Our results indicate the trends toward the expansion of laparoscopic approaches to technically demanding procedures and an increased use of laparoscopic function-preserving surgeries for patients with EGC with acceptable outcomes.

HEPATIC LYMPHOMA AND SPLENIC ASPERGILLOSIS MIMICKING HEPATOSPLENIC ABSCESSES FROM MELIOIDOSIS IN THAILAND.

We report here a case of hepatic lymphoma and splenic aspergillosis in an elderly patient with diabetes mellitus, exhibiting hepatosplenic abscesses mimicking melioidosis. Immunohistochemistry confirmed the diagnosis of a diffuse hepatic large B-cell lymphoma. Biopsy of the spleen revealed a clump of fungus with a slender shape and dichotomous branching, morphologically consistent with aspergillosis. Hepatosplenic abscesses are a common presentation in melioidosis, but this case reveals this assumption can lead to misdiagnosis. Histological and microbiological confirmation are required, especially in patients with hepatosplenic lesions.

Hyperactive STAT5 hijacks T cell receptor signaling and drives immature T cell acute lymphoblastic leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR. Importantly, TCR pathway genes were overexpressed in human T-ALL and mature T cell cancers and activation of TCR pathway kinases was STAT5 dependent. We confirmed STAT5 binding to these genes using ChIP-Seq analysis in human T-ALL cells, which were sensitive to pharmacologic inhibition by dual STAT3/5 degraders or ZAP70 tyrosine kinase blockers in vitro and in vivo. We provide genetic and biochemical proof that STAT5A and STAT5B hyperactivation can initiate T-ALL through TCR pathway hijacking and suggest similar mechanisms for other T cell cancers. Thus, STAT5 or TCR component blockade are targeted therapy options, particularly in patients with chemoresistant clones carrying STAT5BN642H.

Adherence to COVID-19 preventive measures among residents in selected townships, Yangon Region, Myanmar: a community-based cross-sectional study.

BACKGROUND: To fight the current coronavirus disease (COVID-19) pandemic, many countries have implemented various mitigation measures to contain the spread of the disease. By engaging with health service providers, the community's participation in adherence to preventive measures is certainly required in the implementation of COVID-19 mitigation strategies. Therefore, this study aimed to assess the level of adherence to COVID-19 preventive measures and its associated factors among the residents, Yangon Region, Myanmar. METHODS: A community-based cross-sectional study was carried out among 636 residents in Yangon Region, Myanmar, from October to December 2021. A multistage non-probability sampling method, purposively selected for three townships in Yangon Region and convenience sampling for 212 participants from each township, was applied and the data were collected by face-to-face interviews using structured and pretested questionnaires. Data were entered, coded, and analyzed using IBM SPSS version 25.0. Simple and multiple logistic regression analysis were performed to identify the significant variables of adherence to COVID-19 preventive measures. RESULTS: As a level of adherence to COVID-19 preventive measures, the proportion of residents who had good adherence was 39.3% (95% CI 35.5-43.2%), moderate adherence was 37.6% (95% CI 33.8-41.5%), and poor adherence was 23.1% (95% CI 19.9-26.6%). The age group of 31-40 years (AOR: 3.13, 95% CI 1.62-6.05), 30 years and younger (AOR: 3.22, 95% CI 1.75-5.92), Burmese ethnicity (AOR: 2.52, 95% CI 1.44-4.39), own business (AOR: 3.19, 95% CI 1.15-8.87), high school education level and below (AOR: 1.64, 95% CI 1.02-2.69), less than 280.90 USD of monthly family income (AOR: 1.51, 95% CI 1.01-2.29), low knowledge about COVID-19 (AOR: 1.90, 95% CI 1.26-2.88) were significantly associated with poor adherence to COVID-19 preventive measures. CONCLUSIONS: In this study, nearly one-fourth of the residents were experiencing poor adherence to COVID-19 preventive measures. Therefore, building up the risk communication through the community using widely used mainstream media, the continuation of disease surveillance and announcement of updated information or advice for the public to increase awareness towards COVID-19, and enforcement to follow the recommended directions and regulations of health institutions are vital to consider for improving the adherence to preventive measures against COVID-19 among the residents.

Establishing the Learning Curve of Laparoscopic and Robotic Distal Gastrectomy: a Systematic Review and Meta-Regression Analysis.

BACKGROUND: Minimally invasive distal gastrectomy (MIDG) is non-inferior compared with open distal gastrectomy for gastric cancer. However, MIDG bears a learning curve (LC). This study aims to evaluate the number of cases required to surmount the LC (i.e. NLC) in MIDG. METHODS: PubMed, Embase, Scopus, and the Cochrane Library were systematically searched from inception to August 2022 for studies which reported NLC in MIDG. NLC on reduced-port/single-port MIDG only were separately analysed. Poisson mean (95% confidence interval (CI)) was used to determine NLC. Negative binomial regression was used to compare NLC between laparoscopic distal gastrectomy (LDG) and robotic distal gastrectomy (RDG). RESULTS: A total of 45 articles with 71 data sets (LDG n=47, RDG n=24) were analysed. There were 7776 patients in total (LDG n=5516, RDG n=2260). Majority of studies were conducted in East Asia (n=68/71). Majority (76.1%) of data sets used non-arbitrary methods of analyses. The overall NLC for RDG was significantly lower compared to LDG (RDG 22.4 (95% CI: 20.4-24.5); LDG 46.7 (95% CI: 44.1-49.4); incidence rate ratio 0.48, p<0.001). The median number of laparoscopic gastrectomy (LG) cases prior was 0 (interquartile range (IQR) 0-105) for LDG and 159 (IQR 101-305.3) for RDG. Meta-regression analysis did not show a significant impact prior experience in LG, extent of lymphadenectomy and intracorporeal vs extracorporeal anastomosis had on overall NLC for LDG and RDG. CONCLUSION: NLC for RDG is shorter compared to LDG, but this may be due to prior experience in LG and ergonomic advantages of RDG.