Background:
Telemedicine, or healthcare delivery from a distance, has evolved over the past 50 years and helped alter health care delivery to patients around the globe. Its integration into numerous ...domains has permitted high quality care that transcends obstacles of geographic distance, lack of access to health care providers, and cost. Ultrasound is an effective diagnostic tool and its application within telemedicine (“tele-ultrasound”) has advanced substantially in recent years, particularly in high-income settings. However, the utility of tele-ultrasound in resource-limited settings is less firmly established.
Objective:
To determine whether remote tele-ultrasound is a feasible, accurate, and care-altering imaging tool in resource-limited settings.
Data Sources:
PubMed, MEDLINE, and Embase.
Study Eligibility Criteria:
Twelve original articles met the following eligibility criteria: full manuscript available, written in English, including a direct patient-care intervention, performed in a resource-limited setting, images sent to a remote expert reader for interpretation and feedback, contained objective data on the impact of tele-ultrasound.
Study Appraisal and Synthesis Methods:
Abstracts were independently screened by two authors against inclusion criteria for full-text review. Any discrepancies were settled by a senior author. Data was extracted from each study using a modified Cochrane Consumers and Communication Review Group's data extraction template. Study bias was evaluated using the ROBINS-I tool.
Results:
The study results reflect the diverse applications of tele-ultrasound in low-resource settings. Africa was the most common study location. The specialties of cardiology and obstetrics comprised most studies. Two studies primarily relied on smartphones for image recording and transmission. Real-time, rather than asynchronous, tele-ultrasound image interpretation occurred in five of the 12 studies. The most common outcome measures were image quality, telemedicine system requirements, diagnostic accuracy, and changes in clinical management.
Limitations:
The studies included were of poor quality with a dearth of randomized control trials and with significant between study heterogeneity which resulted in incomplete data and made cross study comparison difficult.
Conclusions and Implications of Key Findings:
Low-quality evidence suggests that ultrasound images acquired in resource-limited settings and transmitted using a telemedical platform to an expert interpreter are of satisfactory quality and value for clinical diagnosis and management.
Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, ...we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis.
Background
The decriminalization of marijuana and legalization of derived products requires investigation of their effect on healthcare-related outcomes. Unfortunately, little data are available on ...the impact of marijuana use on surgical outcomes. We aimed to determine the effect of marijuana use on 30-day complications and 1-year weight loss following laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG).
Methods
At a large academic center, 1176 consecutive patients undergoing primary bariatric surgery from 2012 to 2017 were identified and separated into cohorts according to marijuana use. The only exclusions were 19 patients lost to follow-up. Propensity score matching, using logistic regression according to preoperative age, gender, BMI, and comorbid conditions, yielded 73 patient pairs for the control and study arms. All patients were followed two years postoperatively.
Results
Excess BMI lost did not differ between marijuana users and controls at 3 weeks (23.0% vs 18.9%,
p
= 0.095), 3 months (42.0% vs 38.1%,
p
= 0.416), 6 months (60.6% vs 63.1%,
p
= 0.631), 1 year (78.2% vs 77.3%,
p
= 0.789), or 2 years (89.1% vs 74.5%,
p
= 0.604). No differences in the rate of major 30-day postoperative complications, including readmission, infection, thromboembolic events, bleeding events and reoperation rates, were found between groups. Follow-up rate at two years was lower in marijuana users (12.3% vs 27.4%,
p
= 0.023).
Conclusion
This study suggests marijuana use has no impact on 30-day complications or weight loss following bariatric surgery, and should not be a contraindication to bariatric surgery.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer that has proven refractory to immunotherapy. Previously, treatment with the DNA hypomethylating drug decitabine (5-aza-dC; DAC) extended ...survival in the KPC-Brca1 mouse model of PDAC. Here we investigated the effects of DAC in the original KPC model and tested combination therapy with DAC followed by immune checkpoint inhibitors (ICI). Four protocols were tested: PBS vehicle, DAC, ICI (anti-PD-1 or anti-VISTA), and DAC followed by ICI. For each single-agent and combination treatment, tumor growth was measured by serial ultrasound, tumor-infiltrating lymphoid and myeloid cells were characterized, and overall survival was assessed. Single-agent DAC led to increased CD4
and CD8
tumor-infiltrating lymphocytes (TIL), PD1 expression, and tumor necrosis while slowing tumor growth and modestly increasing mouse survival without systemic toxicity. RNA-sequencing of DAC-treated tumors revealed increased expression of Chi3l3 (Ym1), reflecting an increase in a subset of tumor-infiltrating M2-polarized macrophages. While ICI alone had modest effects, DAC followed by either of ICI therapies additively inhibited tumor growth and prolonged mouse survival. The best results were obtained using DAC followed by anti-PD-1, which extended mean survival from 26 to 54 days (
< 0.0001). In summary, low-dose DAC inhibits tumor growth and increases both TILs and a subset of tumor-infiltrating M2-polarized macrophages in the KPC model of PDAC, and DAC followed by anti-PD-1 substantially prolongs survival. Because M2-polarized macrophages are predicted to antagonize antitumor effects, targeting these cells may be important to enhance the efficacy of combination therapy with DAC plus ICI. SIGNIFICANCE: In a pancreatic cancer model, a DNA hypomethylating drug increases tumor-infiltrating effector T cells, increases a subset of M2 macrophages, and significantly prolongs survival in combination with immune checkpoint inhibitors.
.
The role of infection and chronic inflammation in plasma cell disorders (PCD) has been well-described. Despite not being a diagnostic criterion, infection is a common complication of most PCD and ...represents a significant cause of morbidity and mortality in this population. As immune-based therapeutic agents are being increasingly used in multiple myeloma, it is important to recognize their impact on the epidemiology of infections and to identify preventive measures to improve outcomes. This review outlines the multiple factors attributed to the high infectious risk in PCD (e.g. the underlying disease status, patient age and comorbidities, and myeloma-directed treatment), with the aim of highlighting future prophylactic and preventive strategies that could be implemented in the clinic. Beyond this, infection and pathogens as an entity are believed to also influence disease biology from initiation to response to treatment and progression through a complex interplay involving pathogen exposure, chronic inflammation, and immune response. This review will outline both the direct and indirect role played by oncogenic pathogens in PCD, highlight the requirement for large-scale studies to decipher the precise implication of the microbiome and direct pathogens in the natural history of myeloma and its precursor disease states, and understand how, in turn, pathogens shape plasma cell biology.
Purpose
While over 200 million opioid prescriptions are written annually for chronic pain in the USA, little has been written on the impact of opioids on bariatric surgery, specifically on the ...effects of prescription opioid use on weight loss post laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG).
Materials and Methods
We completed a matched-cohort, retrospective review in 1176 consecutive patients undergoing primary bariatric surgery at a single institution. Patients were grouped into chronic prescription opioid users (POU), defined as ongoing opioid use for > 3 months at the time of surgery, and opioid-naïve controls (CON), defined as no opioid use prior to surgery. About 130 POU and 130 CON patients were then matched according to preoperative comorbid conditions and demographics.
Results
Percent total weight loss was similar at 3 weeks, 3 months, 6 months, 1 year, and 2 years in POU and CON—9.6 ± 5.8 vs 8.9 ± 4.5 (
p
= 0.057), 18.4 ± 7.2 vs 18.5 ± 7.2% (
p
= 0.901), 28.0 ± 9.4 vs 27.9 ± 12.9% (
p
= 0.894), 30.3 ± 13.0 vs 32.8 ± 9.0% (
p
= 0.387), and 31.4 ± 12.7 vs 36.9 ± 21.3% (
p
= 0.369), respectively. The 30-day readmission, reoperation, venothrombotic event rate, bleeding rate, and infection rate were similar in POU compared to CON patients.
Conclusions
Complications and weight loss outcomes are similar for prescription opioid users compared to opioid-naïve controls following bariatric surgery. Chronic prescription opioid use is not a contraindication to bariatric surgery.
Chromosome 1 (chr1) copy number abnormalities (CNAs) and structural variants (SV) are frequent in newly diagnosed multiple myeloma (NDMM) and associate with a heterogeneous impact on outcome the ...drivers of which are largely unknown.
A multiomic approach comprising CRISPR, gene mapping of CNA and SV, methylation, expression, and mutational analysis was used to document the extent of chr1 molecular variants and their impact on pathway utilisation.
We identified two distinct groups of gain(1q): focal gains associated with limited gene expression changes and a neutral prognosis, and whole-arm gains, which associate with substantial gene expression changes, complex genetics and an adverse prognosis. CRISPR identified a number of dependencies on chr1 but only limited variants associated with acquired CNAs. We identified seven regions of deletion, nine of gain, three of chromothripsis (CT) and two of templated-insertion (TI), which contain a number of potential drivers. An additional mechanism involving hypomethylation of genes at 1q may contribute to the aberrant gene expression of a number of genes. Expression changes associated with whole-arm gains were substantial and gene set enrichment analysis identified metabolic processes, apoptotic resistance, signaling via the MAPK pathway, and upregulation of transcription factors as being key drivers of the adverse prognosis associated with these variants.
Multiple layers of genetic complexity impact the phenotype associated with CNAs on chr1 to generate its associated clinical phenotype. Whole-arm gains of 1q are the critically important prognostic group that deregulate multiple pathways, which may offer therapeutic vulnerabilities.
Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly. Limiting unnecessary blood ...product transfusions reduces transfusion-related adverse events, financial cost, and delays in care. We assessed the impact of lowering prophylactic platelet administration threshold on blood product utilization patterns and bleeding events. This quasi-experimental study was conducted in an urban academic tertiary medical center. The study population included patients with platelet counts ≥ 10,000/µL and < 50,000/µL undergoing PICC placement in 2018 and 2019 when the minimum platelet thresholds were 50,000/µL and 10,000/µL, respectively. The primary outcome was blood product utilization and the secondary outcome was PICC insertion-related bleeding complications. Thirty-five patients using the 10,000/µL (10 K) platelet threshold and 46 patients using the 50,000/µL (50 K) platelet threshold were enrolled. The 50 K group received more platelets before PICC insertion (0.870 ± 0.885 and 0.143 ± 0.430 pools of platelets-per-person,
p
< 0.001). No patients experienced clinically significant bleeding. Immediately following PICC insertion, minor bleeding occurred in five patients (two 4.3% and three 8.6% in the 50 K and 10 K groups, respectively). Bleeding rates between the two cohorts did not differ (
p
= 0.647). Lowering the minimum platelet threshold from 50,000/µL to 10,000/µL resulted in less prophylactic platelet and total blood product administration with no appreciable difference in PICC insertion-related bleeding.
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