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The Cochrane Database of Systematic... Apr 2023Cystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs, pancreas, and digestive system. Airway clearance techniques (ACTs), traditionally referred to as chest physiotherapy, are recommended as part of a complex treatment programme for people with CF. The aim of an ACTs is to enhance mucociliary clearance and remove viscous secretions from the airways within the lung to prevent distal airway obstruction. This reduces the infective burden and associated inflammatory effects on the airway epithelia. There are a number of recognised ACTs, none of which have shown superiority in improving short-term outcomes related to mucus transport. This systematic review, which has been updated regularly since it was first published in 2000, considers the efficacy of ACTs compared to not performing any ACT in adults and children with CF. It is important to continue to review this evidence, particularly the long-term outcomes, given the recent introduction of highly effective modulator therapies and the improved health outcomes and potential changes to CF management associated with these drugs.
OBJECTIVES
To determine the effectiveness and acceptability of airway clearance techniques compared to no airway clearance techniques or cough alone in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings, to 17 October 2022. We searched ongoing trials registers (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) to 7 November 2022.
SELECTION CRITERIA
We included randomised or quasi-randomised studies that compared airway clearance techniques (chest physiotherapy) with no airway clearance techniques or spontaneous cough alone in people with CF.
DATA COLLECTION AND ANALYSIS
Both review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of the included studies. We used GRADE methodology to assess the certainty of the evidence.
MAIN RESULTS
We included 11 cross-over studies (153 participants) and one parallel study (41 participants). There were differences between studies in how the interventions were delivered, with several intervention groups combining more than one ACT. One study used autogenic drainage; five used conventional chest physiotherapy; nine used positive expiratory pressure (PEP), with one study varying the water pressure between arms; three studies used oscillating PEP; two used exercise; and two used high-frequency chest wall oscillation (HFCWO). Of the 12 included studies, 10 were single-treatment studies, and two delivered the intervention over two consecutive days (once daily in one study, twice daily in the second). This substantial heterogeneity in the treatment interventions precluded pooling of data for meta-analysis. Blinding of participants, caregivers, and clinicians is impossible in airway clearance studies; we therefore judged all studies at unclear risk of performance bias. Lack of information in eight studies made assessment of risk of bias unclear for most other domains. We rated the certainty of evidence as low or very low due to the short-term cross-over trial design, small numbers of participants, and uncertain risk of bias across most or all domains. Six studies (84 participants) reported no effect on pulmonary function variables following intervention; but one study (14 participants) reported an improvement in pulmonary function following the intervention in some of the treatment groups. Two studies reported lung clearance index: one (41 participants) found a variable response to treatment with HFCWO, whilst another (15 participants) found no effect on lung clearance index with PEP therapy (low-certainty evidence). Five studies (55 participants) reported that ACTs, including coughing, increased radioactive tracer clearance compared to control, while a further study (eight participants) reported no improvement in radioactive tracer clearance when comparing PEP to control, although coughing was discouraged during the PEP intervention. We rated the certainty of evidence on the effect of ACTs on radioactive tracer clearance as very low. Four studies (46 participants) investigated the weight of mucus cleared from the lungs and reported greater secretions during chest physiotherapy compared to a control. One study (18 participants) reported no differences in sputum weight (very low-certainty evidence).
AUTHORS' CONCLUSIONS
The evidence from this review shows that ACTs may have short-term effects on increasing mucus transport in people with CF. All included studies had short-term follow-up; consequently, we were unable to draw any conclusions on the long-term effects of ACTs compared to no ACTs in people with CF. The evidence in this review represents the use of airway clearance techniques in a CF population before widespread use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Further research is needed to determine the effectiveness and acceptability of airway clearance in those treated with highly effective CFTR modulators.
Topics: Adult; Child; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Cough; Radioactive Tracers; Forced Expiratory Volume
PubMed: 37042825
DOI: 10.1002/14651858.CD001401.pub4 -
Journal of Oncology 2023Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated... (Review)
Review
BACKGROUND
Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency.
METHODS
The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated.
RESULTS
A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04-1.67, = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96-2.10, = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09-1.87, = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01-2.57, = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09-1.79, = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models.
CONCLUSION
Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.
PubMed: 36733671
DOI: 10.1155/2023/5957481 -
Bone Marrow Transplantation Apr 2023Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD... (Review)
Review
Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy. Our patient achieved a complete response (CR) with limited toxicity but experienced a CD19 relapse 8 months after infusion despite CAR-T persistence. Literature review revealed 14 DLBCL and 2 Burkitt lymphoma PTLD cases treated with CD19 CAR-T cells. Kidney (n = 12), liver (n = 2), heart (n = 2), and pancreas after kidney (n = 1) transplant recipients were analyzed. The objective response rate (ORR) was 82.4% (14/17), with 58.5% (10/17) CRs and a 6.5-month median duration of response. Among kidney transplant recipients, the ORR was 91.7% (11/12). Allograft rejection occurred in 23.5% (4/17). No graft failure occurred. Our analysis suggests that CD19 CAR-T therapy offers short-term effectiveness and manageable toxicity in SOTRs with R/R PTLD. Further investigation through larger datasets and prospective study is needed.
Topics: Humans; Antigens, CD19; Epstein-Barr Virus Infections; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Neoplasm Recurrence, Local; Organ Transplantation; Receptors, Chimeric Antigen; Transplant Recipients
PubMed: 36575360
DOI: 10.1038/s41409-022-01907-z -
Annals of Surgery May 2023To conduct a systematic review and meta-analysis of randomized controlled trials compared laparoscopic pancreatoduodenectomy (LPD) versus open pancreatoduodenectomy... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review and meta-analysis of randomized controlled trials compared laparoscopic pancreatoduodenectomy (LPD) versus open pancreatoduodenectomy (OPD) in patients with periampullary tumors.
BACKGROUND
LPD has gained attention; however, its safety and efficacy versus OPD remain debatable.
METHODS
We searched PubMed and Embase. Primary outcomes were the length of hospital stay (LOS) (day), Clavien-Dindo grade ≥III complications, and 90-day mortality. Secondary outcomes were blood loss (milliliter), blood transfusion, duration of operation (minute), readmission, reoperation, comprehensive complication index score, bile leak, gastrojejunostomy or duodenojejunostomy leak, postoperative pancreatic fistula, postpancreatectomy hemorrhage, delayed gastric emptying, surgical site infection, intra-abdominal infection, number of harvested lymph nodes, and R0 resection. Pooled odds ratio (OR) or mean difference (MD) of data was calculated using the random-effect model. The grading of recommendations, assessment, development and evaluation approach was used for grading the level of evidence.
RESULTS
Four randomized controlled trials yielding 818 patients were included, of which 411 and 407 patients underwent LPD and OPD, respectively. The meta-analysis concluded that 2 approaches were similar, except in the LPD group, the LOS tended to be shorter [MD=-2.54 (-5.17, 0.09), P =0.06], LOS in ICU was shorter [MD=-1 (-1.8, -0.2), P =0.01], duration of operation was longer [MD=75.16 (23.29, 127.03), P =0.005], blood loss was lower [MD=-115.40 (-152.13, -78.68), P <0.00001], blood transfusion was lower [OR=0.66 (0.47, 0.92), P =0.01], and surgical site infection was lower [OR=0.35 (0.12, 0.96), P =0.04]. The overall certainty of the evidence was moderate.
CONCLUSIONS
Within the hands of highly skilled surgeons in high-volume centers, LPD is feasible and as safe and efficient as OPD.
Topics: Humans; Pancreaticoduodenectomy; Pancreas; Pancreatic Neoplasms; Pancreatic Fistula; Surgical Wound Infection; Laparoscopy; Postoperative Complications; Length of Stay; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 36519444
DOI: 10.1097/SLA.0000000000005785 -
Annals of Gastroenterology 2022Percutaneous endoscopic gastrostomy (PEG) and percutaneous radiological gastrostomy (PRG) are invasive interventions used for enteral access. We performed a systematic...
BACKGROUND
Percutaneous endoscopic gastrostomy (PEG) and percutaneous radiological gastrostomy (PRG) are invasive interventions used for enteral access. We performed a systematic review and meta-analysis with assessment of certainty of evidence to compare the risk of adverse outcomes and technical failure between PEG and PRG.
METHODS
We queried PubMed, EMBASE, and Cochrane from inception through January 2022 to identify studies comparing outcomes of PEG and PRG. The primary outcome was 30-day all-cause mortality; secondary outcomes included the risk of colon perforation, peritonitis, bleeding, technical failure, peristomal infections, and tube-related complications. We performed GRADE assessment to assess the certainty of evidence and leave-one-out analysis for sensitivity analysis.
RESULTS
In the final analysis, 33 studies, including 26 high-quality studies, provided data on 275,117 patients undergoing PEG and 192,691 patients undergoing PRG. Data from high quality studies demonstrated that, compared to PRG, PEG had significantly lower odds of selected outcomes, including 30-day all-cause mortality (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60-0.95; P=0.02), colon perforation (OR 0.61, 95%CI 0.49-0.75; P<0.001), and peritonitis (OR 0.71, 95%CI 0.63-0.81; P<0.001). There was no significant difference between PEG and PRG in terms of technical failure, bleeding, peristomal infections or mechanical complications. The certainty of the evidence was rated moderate for colon perforation and low for all other outcomes.
CONCLUSIONS
PEG is associated with a significantly lower risk of 30-day all-cause mortality, colon perforation, and peritonitis compared to PRG, while having a comparable technical failure rate. PEG should be considered as the first-line technique for enteral access.
PubMed: 36406969
DOI: 10.20524/aog.2022.0752 -
Gastrointestinal Endoscopy Mar 2023Previous studies have demonstrated that the ideal time for drainage of walled-off pancreatic fluid collections is 4 to 6 weeks after their development. However, some... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Previous studies have demonstrated that the ideal time for drainage of walled-off pancreatic fluid collections is 4 to 6 weeks after their development. However, some pancreatic collections, notably infected pancreatic fluid collections, require earlier drainage. Nevertheless, the optimal timing of the first intervention is unclear, and consensus data are sparse. The aim of this study was to evaluate the clinical efficacy and safety of EUS-guided drainage of pancreatic fluid collections <4 weeks after development compared with ≥4 weeks after development.
METHODS
Search strategies were developed for PubMed, Embase, and Cochrane Library databases from inception. Outcomes of interest were technical success, defined as successful endoscopic placement of a lumen-apposing metal stent; clinical success, defined as a reduction in cystic collection size; and procedure-related adverse events. A random-effects model was used for analysis, and results are expressed as odds ratio (OR) with 95% confidence interval (CI).
RESULTS
Six studies (630 patients) were included in our final analysis, in which 182 patients (28.9%) were enrolled in the early drainage cohort and 448 patients (71.1%) in the standard drainage cohort. The mean fluid collection size was 143.4 ± 18.8 mm for the early cohort versus 128 ± 19.7 mm for the standard cohort. Overall, technical success was equal in both cohorts. Clinical success did not favor either standard drainage or early drainage (OR, .39; 95% CI, .13-1.22; P = .11). No statistically significant differences were found in overall adverse events (OR, 1.67; 95% CI, .63-4.45; P = .31) or mortality (OR, 1.14; 95% CI, .29-4.48; P = .85). Hospital stay was longer for patients undergoing early drainage compared with standard drainage (23.7 vs 16.0 days, respectively).
CONCLUSIONS
Both early (<4 weeks) and standard (≥4 weeks) drainage of walled-off pancreatic fluid collections offer similar technical and clinical outcomes. Patients requiring endoscopic drainage should not be delayed for 4 weeks.
Topics: Humans; Pancreatic Pseudocyst; Pancreas; Endoscopy; Stents; Treatment Outcome; Drainage; Endosonography
PubMed: 36395824
DOI: 10.1016/j.gie.2022.11.003 -
HPB : the Official Journal of the... Dec 2022Surgical site infections (SSI) cause significant morbidity. Prophylactic negative pressure wound therapy (NPWT) may promote wound healing and decrease SSI. The objective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical site infections (SSI) cause significant morbidity. Prophylactic negative pressure wound therapy (NPWT) may promote wound healing and decrease SSI. The objective is to evaluate the effect of prophylactic NPWT on SSI in patients undergoing pancreatectomy.
METHODS
Electronic databases were searched from inception until April 2022. Randomized controlled trials (RCTs) comparing prophylactic NPWT to standard dressings in patients undergoing pancreatectomy were included. The primary outcome was the risk of SSI. Secondary outcomes included the risk of superficial and deep SSI and organ space infection (OSI). Random effects models were used for meta-analysis.
RESULTS
Four single-centre RCTs including 309 patients were identified. Three studies were industry-sponsored, and two were at high risk of bias. There was no significant difference in the risk of SSI in patients receiving NPWT vs. control (14% vs. 21%, RR = 0.72, 95%CI = 0.32-1.60, p = 0.42, I = 53%). Likewise, there was no significant difference in the risk of superficial and deep SSI or OSI. No significant difference was found on subgroup analysis of patients at high risk of wound infection or on sensitivity analysis of studies at low risk of bias.
CONCLUSION
Prophylactic NPWT does not significantly decrease the risk of SSI among patients undergoing pancreatectomy. Insufficient evidence exists to justify the routine use of NPWT.
Topics: Humans; Negative-Pressure Wound Therapy; Surgical Wound Infection; Bandages; Wound Healing; Pancreatectomy
PubMed: 36244906
DOI: 10.1016/j.hpb.2022.08.010 -
Cureus Aug 2022() bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal... (Review)
Review
() bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal data. Little is known about the risk factors involved with this malignancy. In this systematic review, we aimed to examine the relationship between infection and pancreatic cancer based on the evidence from the existing observational studies across the world. We searched major electronic databases such as PubMed, MEDLINE, Science Direct, and Cochrane Library. After a careful and thorough screening process, we selected 15 observation studies for this systematic review. Six of 15 studies found a significant association between infection and pancreatic cancer. Additionally, four of these studies found a significant relationship between the cytotoxin-associated gene A strain of and pancreatic cancer. Based on the evidence from the selected studies, a weak association was observed between infection and cancer of the pancreas, especially in European and Asian populations compared to the North American population. The cross-sectional evidence from the case-control studies only suggests the existence of an association but does not provide substantial evidence of the causative relationship. Further large-scale, prospective cohort studies are warranted in the future to understand this contradictory relationship better.
PubMed: 36185865
DOI: 10.7759/cureus.28543 -
Cureus Aug 2022There is increasing literature mentioning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19 infection) causing acute pancreatitis (AP). It... (Review)
Review
There is increasing literature mentioning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19 infection) causing acute pancreatitis (AP). It is hypothesized that SARS-Cov-2 causes pancreatic injury either by direct cytotoxic effect of the virus on pancreatic cells through the angiotensin-converting enzyme 2 (ACE2) receptors - the main receptors for the virus located on pancreatic cells - or by the cytokine storm that results from COVID-19 infection or a component of both. Many viruses are related to AP including mumps, coxsackievirus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and as data evolves SARS-CoV-2 virus may be one of them as well. We conducted a systematic literature review to explore the current literature and provide an overview of the evidence of AP in COVID-19 infection. We studied the presence of AP in patients with SARS-CoV-2 infection and calculated the time of diagnosis of SARS-CoV-2 infection with respect to the time of diagnosis of AP. We also studied the age, gender, clinical manifestations, time of onset of symptoms, laboratory values, imaging findings, mortality, length of stay, comorbidities, need for Intensive Care Unit (ICU) care, and excluded any other common causes of AP. We included 40 articles comprising 46 patients. All patients had a positive SARS-CoV-2 polymerase chain reaction (PCR) test and all patients had AP as per Atlanta's criteria. The most common clinical presentation was abdominal pain in 29 (63.0%). Edematous pancreas was the most common Computed Tomography Abdomen Pelvis (CTAP) scan finding in these patients (35 patients). Seventeen (37%) patients required ICU admission and six (13%) patients died. Our study provides an important overview of the available data on AP in COVID-19 patients and concludes that AP is an important complication in COVID-19 infection and should be considered as an important differential in patients with COVID-19 infection who complain of abdominal pain.
PubMed: 36168341
DOI: 10.7759/cureus.28380 -
Vaccines Aug 2022Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event... (Review)
Review
BACKGROUND
Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ.
OBJECTIVES
To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection.
METHODS
For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction.
RESULTS
One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male ( = 51, 53.1%) and were of White (Caucasian) ( = 51, 53.7%) and Hispanic ( = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech ( = 31), Moderna ( = 14), Oxford Uni-AstraZeneca ( = 10) and Sinovac-CoronaVac ( = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2-17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5-21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success ( = 70, 85.4%), graft failure ( = 12, 14.6%), survived ( = 90, 95.7%) and died ( = 4, 4.3%)].
CONCLUSION
The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
PubMed: 36016180
DOI: 10.3390/vaccines10081289