Complications due to spontaneous septostomy of the dividing membrane in monochorionic diamniotic pregnancies are rarely described. Herein, we report the case of a preterm female neonate from a monochorionic diamniotic twin pregnancy delivered by caesarean section at 32 weeks of gestation. She was born with a broad band of a transparent membrane-like material firmly attached to her lower abdomen. Postnatally, she developed respiratory distress syndrome and persistent pulmonary hypertension, complicated by bilateral pneumothorax. She died due to respiratory failure when she was 1 day old. Her twin sister survived with no malformations. At postmortem examination, the neonate had severe lung hypoplasia, and the attached material was diagnosed as the dividing septum. We hypothesize that the lung hypoplasia was secondary to local oligohydramnios, which developed as a consequence of the twin being firmly stuck in the defect of the dividing membrane. To our best knowledge, spontaneous septostomy causing an ultimately fatal amniotic band syndrome has not previously been described.
http://bit.ly/2TcHAw2
Σάββατο 29 Δεκεμβρίου 2018
Spontaneous Septostomy in a Twin Pregnancy Causing Fatal Amniotic Band Syndrome
Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group
Abstract
Background
Even clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting.
Methods
NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany.
Discussion
The NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research.
Trial registration
ClinicalTrials.gov: NCT02047513, 08/13/2014.
http://bit.ly/2EVHo13
Clinical characteristics and treatment outcomes in six cases of malignant tenosynovial giant cell tumor: initial experience of molecularly targeted therapy
Abstract
Background
Although tenosynovial giant cell tumor (TGCT) is classified as a benign tumor, it may undergo malignant transformation and metastasize in extremely rare occasions. High aberrant expression of CSF1 has been implicated in the development of TGCT and recent studies have shown promising activity of several CSF1R inhibitors against benign diffuse-type TGCT; however, little is known about their effects in malignant TGCT.
Case presentation
Information from six consenting patients (3 men, 3 women) with malignant TGCT presenting to Dana-Farber Cancer Institute for initial or subsequent consultation was collected. Median age at initial diagnosis of TGCT was 49.5 years (range 12–55), and median age at diagnosis of malignant TGCT was 50 years (range 34–55). Two patients developed malignant TGCT de novo, while four other cases showed metachronous malignant transformation. All tumors arose in the lower extremities (3 knee, 2 thigh, 1 hip). Five patients underwent surgery for the primary tumors, and four developed local recurrence. All six patients developed lung metastases, and four of five evaluable tumors developed inguinal and pelvic lymph node metastases. All six patients received systemic therapy. Five patients were treated with at least one tyrosine kinase inhibitor with inhibitory activity against CSF1R; however, only one patient showed clinical benefit (SD or PR). Five patients were treated with conventional cytotoxic agents. Doxorubicin-based treatment showed clinical benefit in all four evaluable patients, and gemcitabine/docetaxel showed clinical benefit in two patients. All six patients died of disease after a median of 21.5 months from diagnosis of malignant TGCT.
Conclusions
This study confirms that TGCT may transform into an aggressive malignant tumor. Lymph node and pulmonary metastases are common. Local recurrence rates are exceedingly high. Conventional cytotoxic chemotherapy showed clinical benefit, whereas tyrosine kinase inhibitors against CSF1R showed limited activity. Given its rarity, a prospective registry of malignant TGCT patients is needed to further understand the entity and to develop effective strategies for systemic treatment.
http://bit.ly/2EWabBH
KRas4B-PDE6δ complex stabilization by small molecules obtained by virtual screening affects Ras signaling in pancreatic cancer
Abstract
Background
The GTPase KRas4B has been utilized as a principal target in the development of anticancer drugs. PDE6δ transports KRas4B to the plasma membrane, where it is released to activate various signaling pathways required for the initiation and maintenance of cancer. Therefore, identifying new small molecules that prevent activation of this GTPase by stabilizing the KRas4B-PDE6δ molecular complex is a practical strategy to fight against cancer.
Methods
The crystal structure of the KRas4B-PDE6δ heterodimer was employed to locate possible specific binding sites at the protein-protein interface region. Virtual screening of Enamine-database compounds was performed on the located potential binding sites to identify ligands able to simultaneously bind to the KRas4B-PDE6δ heterodimer. A molecular dynamics approach was used to estimate the binding free-energy of the complex. Cell viability and apoptosis were measured by flow cytometry. G-LISA was used to measure Ras inactivation. Western blot was used to measure AKT and ERK activation. MIA PaCa-2 cells implanted subcutaneously into nude mice were treated with D14 or C22 and tumor volumes were recorded.
Results
According to the binding affinity estimation, D14 and C22 stabilized the protein-protein interaction in the KRas4B-PDE6δ complex based on in vitro evaluation of the 38 compounds showing antineoplastic activity against pancreatic MIA PaCa-2 cancer cells. In this work, we further investigated the antineoplastic cellular properties of two of them, termed D14 and C22, which reduced the viability in the human pancreatic cancer cells lines MIA PaCa-2, PanC-1 and BxPC-3, but not in the normal pancreatic cell line hTERT-HPNE. Compounds D14 and C22 induced cellular death via apoptosis. D14 and C22 significantly decreased Ras-GTP activity by 33% in MIA PaCa-2 cells. Moreover, D14 decreased AKT phosphorylation by 70% and ERK phosphorylation by 51%, while compound C22 reduced AKT phosphorylation by 60% and ERK phosphorylation by 36%. In addition, compounds C22 and D14 significantly reduced tumor growth by 88.6 and 65.9%, respectively, in a mouse xenograft model.
Conclusions
We identified two promising compounds, D14 and C22, that might be useful as therapeutic drugs for pancreatic ductal adenocarcinoma treatment.
http://bit.ly/2EZzhAC
Symptomatic venous thromboembolism associated with peripherally inserted central catheters predicts a worse survival in nasopharyngeal carcinoma: results of a large cohort, propensity score–matched analysis
Abstract
Background
Despite increasing use, symptomatic venous thromboembolism (VTE) associated with peripherally inserted central catheter (PICC) is a common complication in nonmetastatic nasopharyngeal carcinoma (NPC) patients.
Methods
A total of 3012 nonmetastatic NPC patients were enrolled in this retrospective study, and we applied Cox regression and log-rank tests to assess the association between PICC-VTE and survival using the propensity score method (PSM) to adjust for gender, age, radiotherapy technique, tumor stage, node stage, UICC clinical stage and pre-treatment EBV DNA.
Results
217 patients developed PICC-VTE, with an incidence of 7.20%. PSM identified 213 patients in the cohort with VTE and 852 in that without. Patients who developed PICC-VTE had a shorter 5-year PFS (77.5% vs 87.6%, p < 0.001), DMFS (85.0% vs 91.2%, p < 0.001), LRRFS (93.9% vs 97.7%, p < 0.001) and OS (85.4% vs 87.6%, p < 0.001). Subgroup analyses indicated that no significant survival difference was found between PICC-related superficial venous thrombosis and deep vein thrombosis, nor did different anticoagulant treatment methods.
Conclusions
PICC-VTE was associated with a worse survival outcome in nonmetastatic NPC patients. A prospective randomized clinical trial is required to verify the results.
http://bit.ly/2ESBQnk
A scoring system to predict local progression-free survival in patients irradiated with 20 Gy in 5 fractions for malignant spinal cord compression
Abstract
Background
Local progression-free survival (LPFS = stable or improved motor function/resolution of paraplegia during RT without in-field recurrence following RT) is important when treating metastatic spinal cord compression (MSCC). An instrument to estimate LPFS was created to identify patients appropriately treated with short-course RT instead of longer-course RT plus/minus decompressive surgery.
Methods
In 686 patients treated with 20 Gy in 5 fractions alone, ten characteristics were retrospectively analyzed for LPFS including age, interval between tumor diagnosis and RT of MSCC, visceral metastases, other bone metastases, primary tumor type, gender, time developing motor deficits, pre-RT gait function, number of vertebrae affected by MSCC, and performance score. Characteristics significantly (p < 0.05) associated with LPFS on multivariate analyses were incorporated in the scoring system. Six-month LPFS rates for significant characteristics were divided by 10, and corresponding points were added.
Results
On multivariate analyses, visceral metastases (p < 0.001), tumor type (p = 0.009), time developing motor deficits (p < 0.001) and performance score (p = 0.009) were associated with LPFS and used for the scoring system. Scores for patients ranged between 24 and 35 points. Three groups were designed: 24–28 (A), 29–31 (B) and 32–35 (C) points. Six-month LPFS rates were 46, 69 and 92%, 12-month LPFS rates 46, 63 and 83%. Median survival times were 2 months (61% died within 2 months), 4 months and ≥ 11 months (median not reached).
Conclusions
Most group A patients appeared sub-optimally treated with 20 Gy in 5 fractions. Patients with survival prognoses ≤2 months may be considered for best supportive care or single-fraction RT, those with prognoses ≥3 months for longer-course RT plus/minus upfront decompressive surgery. Many group B and most group C patients achieved long-time LPFS and appeared sufficiently treated with 20 Gy in 5 fractions. However, based on previous data, long-term survivors may benefit from longer-course RT.
http://bit.ly/2EZzfZw
Outcomes of re-irradiation for brain recurrence after prophylactic or therapeutic whole-brain irradiation for small cell lung Cancer: a retrospective analysis
Abstract
Background
Small cell lung cancer (SCLC) can recur in the brain after whole-brain irradiation (WBI). We documented outcomes after treatment of such recurrences and sought predictors of local control and overall survival (OS).
Materials and methods
Eighty-five patients with SCLC and brain recurrence after prophylactic or therapeutic WBI in 1998–2015 were identified and data were extracted from the medical records. Survival was estimated with the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards modeling was used to identify factors associated with OS or further brain progression.
Results
Brain recurrence was treated by stereotactic radiosurgery (SRS) in 33 patients (39%), repeat WBI in 14 (16%), chemotherapy-only in 16 (19%), and observation in 22 (26%). Median OS time after brain recurrence (OSrec) was 4.3 months for all patients; 6-month OSrec rates were 58% after SRS, 21% after repeat WBI, 50% after chemotherapy-only, and 5% after observation (P < 0.001). Inferior OSrec was associated with poor performance status (ECOG score ≥ 3) and uncontrolled extracranial disease. Superior OSrec was associated with receipt of ≥4 chemotherapy cycles before brain recurrence and receipt of chemotherapy, SRS, or repeat WBI afterward. Receipt of chemotherapy after brain recurrence correlated with brain progression.
Conclusions
Some patients with brain recurrence after WBI for SCLC can survive for extended periods with appropriate intervention, especially those with adequate performance status or controlled extracranial disease.
http://bit.ly/2EWxueX
Classification of triple-negative breast cancers based on Immunogenomic profiling
Abstract
Background
Abundant evidence shows that triple-negative breast cancer (TNBC) is heterogeneous, and many efforts have been devoted to identifying TNBC subtypes on the basis of genomic profiling. However, few studies have explored the classification of TNBC specifically based on immune signatures that may facilitate the optimal stratification of TNBC patients responsive to immunotherapy.
Methods
Using four publicly available TNBC genomics datasets, we classified TNBC on the basis of the immunogenomic profiling of 29 immune signatures. Unsupervised and supervised machine learning methods were used to perform the classification.
Results
We identified three TNBC subtypes that we named Immunity High (Immunity_H), Immunity Medium (Immunity_M), and Immunity Low (Immunity_L) and demonstrated that this classification was reliable and predictable by analyzing multiple different datasets. Immunity_H was characterized by greater immune cell infiltration and anti-tumor immune activities, as well as better survival prognosis compared to the other subtypes. Besides the immune signatures, some cancer-associated pathways were hyperactivated in Immunity_H, including apoptosis, calcium signaling, MAPK signaling, PI3K–Akt signaling, and RAS signaling. In contrast, Immunity_L presented depressed immune signatures and increased activation of cell cycle, Hippo signaling, DNA replication, mismatch repair, cell adhesion molecule binding, spliceosome, adherens junction function, pyrimidine metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and RNA polymerase pathways. Furthermore, we identified a gene co-expression subnetwork centered around five transcription factor (TF) genes (CORO1A, STAT4, BCL11B, ZNF831, and EOMES) specifically significant in the Immunity_H subtype and a subnetwork centered around two TF genes (IRF8 and SPI1) characteristic of the Immunity_L subtype.
Conclusions
The identification of TNBC subtypes based on immune signatures has potential clinical implications for TNBC treatment.
http://bit.ly/2EYeptD
Diagnosis of Systemic Lupus Erythematosus in a Polynesian Male with a History of Rheumatic Fever: A Case Report and Literature Review
The presence of rheumatic heart disease (RHD) and systemic lupus erythematosus (SLE) has rarely been described in one patient. This report describes an adolescent Polynesian male with RHD who developed SLE years later. Initially, he fulfilled modified Jones criteria for rheumatic fever with aortic insufficiency, transient arthritis, elevated streptococcal titers, and a high erythrocyte sedimentation rate with a negative antinuclear antibody (ANA). He responded well to nonsteroidal anti-inflammatory and penicillin prophylaxis, which supported the diagnosis of rheumatic fever. Five years after his RHD diagnosis, he developed pancreatitis with glomerulonephritis, nephrosis, and pancytopenia. In addition, laboratory results revealed that he had multiple autoantibodies: anti-Sm and extremely elevated anti-dsDNA and ANA, fulfilling diagnostic criteria for SLE. The patient was treated, and he responded to pulse steroids followed by oral steroid therapy. To our knowledge, there are no known reported cases of a patient who was diagnosed with both RHD and SLE and met the clinical criteria for both diseases. The rarity of this concurrent disease process in one patient suggests a possible overlap in humoral immunity toward self-antigens as well as ethnic variability that increases predisposition to rheumatologic diseases.
http://bit.ly/2CHhdZF
Mechanical Outcomes, Microleakage, and Marginal Accuracy at the Implant-Abutment Interface of Original versus Nonoriginal Implant Abutments: A Systematic Review of In Vitro Studies
Purpose. Instead of original abutments, compatible abutments are often selected for financial reasons. The present study aimed to evaluate mechanical outcomes, microleakage, and marginal accuracy at the implant-abutment interface of original versus nonoriginal implant abutments. Study Selection. Search strategy encompassed literature from 1967 up to March 2017 to identify relevant studies meeting the inclusion criteria. The following electronic databases were consulted: PubMed database of the U.S. National Library of Medicine, Embase (Excerpta Medica dataBASE), and the Grey Literature Database (New York Academy of Medicine Grey Literature Report). Quality assessment of the full-text articles selected was performed. Abutments were classified in original (produced by the same implant manufacturer), nonoriginal certified (produced by a third-party milling center, certified by implant companies), and nonoriginal compatible (produced by a third-party milling center for similar connections). Results. A total of 16 articles fulfilled inclusion criteria and quality assessment and were selected for the qualitative analysis. All of the included studies were in vitro research with high or moderate risk of bias and reported data from 653 implant abutments. Original and nonoriginal certified abutments showed better results in terms of mechanical outcomes, microleakage, and marginal accuracy compared to nonoriginal compatible abutments. Conclusions. Following the clear warnings coming from the present systematic review, clinical suggestions regarding the effect of a nonoriginal abutment can be drawn. However, in vivo, long-term, randomized controlled trials are needed to provide definitive clinical conclusion about the long-term clinical outcomes of original and nonoriginal abutments.
http://bit.ly/2AlTQmJ
Biomechanical Effects of Incisional Negative Wound Pressure Dressing: An Ex Vivo Model Using Human and Porcine Abdominal Walls
Introduction. Incisional negative pressure wound therapy (iNPWT) has been of recent interest in different surgical fields as beneficial outcomes on high-risk wounds have been reported. Nevertheless, its mechanisms of function are not widely studied to date. Methods. We established two ex vivo setups of iNPWT in porcine and human abdominal wall for measuring pressures within the wound which result from iNPWT application. For pressure measurements, a high-resolution manometry catheter and a balloon catheter probe were used in a wound sealed with either a commercially available PREVENA VAC kit or a self-made iNPWT kit. Furthermore, we evaluated seroma evacuation by iNPWT. Results. Both setups showed similar characteristics of pressure curves within the wound when applying increasing negative pressures. Application of high pressures did not result in a similar increase in wound pressure. Only subtotal evacuation of seroma by iNPWT application (about 75% of volume) could be detected. Conclusion. Our ex vivo model of iNPWT in porcine and human abdominal wall could show reproducible measurements of pressures within the wounds in both types of tissue. As intrawound pressures did not increase in the same way as the applied negative pressure, we suggest that our results do not advocate the idea of using iNPWT for wound care especially as seroma evacuation remains insufficient.
http://bit.ly/2Ssn5LQ
A Novel Scoring System Based on the Level of HDL-C for Predicting the Prognosis of t-DLBCL Patients: A Single Retrospective Study
The t-DLBCL patients are generally regarded to experience a poor prognosis. However, there is little consensus to guide optimal management strategies for such patients group. The present study aimed to explore the incidence of transformation and the prognosis factors for t-DLBCL patients, thereby providing insights for clinical choices. We retrospectively investigated 46 patients with diffuse large B-cell lymphomas (DLBCL) associated with an indolent small B-cell non-Hodgkin lymphoma (iNHL) from January 2007 to June 2017 in our department. In multivariate analysis, bone marrow (BM) involvement and low level of high-density lipoprotein cholesterol (HDL-C) were considered as two negatively and independently prognostic factors for overall survival (OS) (BM: p=0.007, HR 7.475, 95%CI: 1.744-32.028; HDL-C: p=0.032, HR10.037, 95%CI: 1.226-82.162). International Prognostic Index (IPI) risk group was identified as a single independent prognostic factor of progression-free survival (PFS) (p=0.048, HR 2.895, 95%CI: 1.010-8.297). A novel prognostic scoring system named BH model (BH stands for the intertwined initials of BM situation and the level of HDL-C) was further developed to stratify these patients into two risk groups, which performed well. Combining the BH scoring model and IPI scoring system could better predict the outcomes of these patients.
http://bit.ly/2AnB2Uq
Cerebrovascular Complications and Infective Endocarditis: Impact of Available Evidence on Clinical Outcome
Background. Infective endocarditis (IE) is a life-threatening disease. Its epidemiological profile has substantially changed in recent years although 1-year mortality is still high. Despite advances in medical therapy and surgical technique, there is still uncertainty on the best management and on the timing of surgical intervention. The objective of this review is to produce further insight into the short- and long-term outcomes of patients with IE, with a focus on those presenting cerebrovascular complications.
http://bit.ly/2SqQcPH
Review of Hematopathology Consult Cases: A Two-Year Experience in a Tertiary Referral Center in Lebanon
Hematopathology remains a difficult diagnostic field. With the significant ongoing changes in the classification system that happened over the past several decades, the general pathologist faces many challenges when dealing with patients suspected to have lymphoma or leukemia. The authors assessed referred hematopathology cases that were reviewed by specialized hematopathologists. Of 309 cases, major discrepancy was found in 23% of them. The discrepancy ranged from lymphoma reclassification to other major revisions that had significant impact on patient treatment and management. This paper highlights some of the challenges that may face the general practicing pathologist when dealing with suspected hematopoietic neoplasms.
http://bit.ly/2AlzrhT
Necrotizing Soft Tissue Infection: Diagnostic Accuracy of Physical Examination, Imaging, and LRINEC Score: A Systematic Review and Meta-Analysis
Objective: We sought to summarize accuracy of physical examination, imaging, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score in diagnosis of necrotizing soft tissue infection (NSTI) in adults with a soft tissue infection clinically concerning for NSTI. Summary of Background Data: NSTI is a life-threatening diagnosis. Delay to diagnosis and surgical management is associated with increased mortality. Methods: We searched 6 databases from inception through November 2017. We included English-language studies reporting diagnostic accuracy of testing or LRINEC Score. Outcome was NSTI confirmed by surgery or histopathology. Two reviewers screened all citations and extracted data independently. Summary measures were obtained from the Hierarchical Summary Receiver Operating Characteristic model. Results: From 2,290 citations, we included 23 studies (n = 5982). Of physical examination signs, pooled sensitivity and specificity for fever was 46.0% and 77.0% respectively, for hemorrhagic bullae 25.2% and 95.8%, and for hypotension 21.0% and 97.7%. Computed tomography (CT) had sensitivity of 88.5% and specificity of 93.3%, while plain radiography had sensitivity of 48.9% and specificity of 94.0%. Finally, LRINEC ≥ 6 had sensitivity of 68.2% and specificity of 84.8%, while LRINEC ≥ 8 had sensitivity of 40.8% and specificity of 94.9%. Conclusions: Absence of any 1 physical examination feature (eg, fever or hypotension) is not sufficient to rule-out NSTI. CT is superior to plain radiography. LRINEC had poor sensitivity, and should not be used to rule-out NSTI. Given the poor sensitivity of these tests, a high clinical suspicion warrants early surgical consultation for definitive diagnosis and management.http://bit.ly/2QeUOGQ
Cerebrospinal fluid penetration of very high-dose meropenem: a case report
Standard dosing of meropenem (2 g t.i.d.) produces CSF concentrations of only 1–2 mg/L which is inferior to the clinical breakpoint for most Gram-negative bacteria. There is therefore concern that dosing must ...
http://bit.ly/2Q7Xaag
Gancao (Glycyrrhizae Radix) provides the main contribution to Shaoyao-Gancao decoction on enhancements of CYP3A4 and MDR1 expression via pregnane X receptor pathway in vitro
Chinese herbal formula Shaoyao Gancao decoction (SGD) is often used as an adjuvant with chemotherapeutic agents to treat cancer. Due to the herb-drug interactions, the alternations of drug metabolic enzyme and...
http://bit.ly/2ESw6tH
Severe acute pancreatitis with blood infection by Candida glabrata complicated severe agranulocytosis: a case report
Blood infection with Candida glabrata often occurs in during severe acute pancreatitis (SAP). It complicate severe agranulocytosis has not been reported.
http://bit.ly/2EX5o3L
Molecular characterization of an outbreak of enterovirus-associated meningitis in Mossel Bay, South Africa, December 2015–January 2016
Human enteroviruses (HEVs) are common causal agents of aseptic meningitis in young children. Laboratory and syndromic surveillance during December 2015 and January 2016 noted an unusually high number of paedia...
http://bit.ly/2EWdNE3
Association of HIV-infection, antiretroviral treatment and metabolic syndrome with large artery stiffness: a cross-sectional study
Effective combined antiretroviral therapy (cART) has improved life expectancy among people living with HIV-1 infection. Treated HIV-1infection increases the prevalence of metabolic syndrome (MS). Despite sub-S...
http://bit.ly/2ETfbYV
Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses
The emergence of different viral infections during the last decades like dengue, West Nile, SARS, chikungunya, MERS-CoV, Ebola, Zika and Yellow Fever raised some questions on quickness and reliability of labor...
http://bit.ly/2EVSQsQ
Spotted fever rickettsioses causing myocarditis and ARDS: a case from Sri Lanka
Spotted fever group of rickettsial infections are emerging in Sri Lanka. We describe a patient with rapidly progressing ARDS and myocarditis secondary to spotted fever caused by Rickettsia conorii. ARDS and myoca...
http://bit.ly/2EWPG8S
Cover
The cover image is based on the Original Research Long‐term follow‐up of single crowns supported by short, moderately rough implants – A prospective 10‐year cohort study by Fabio Rossi et al., DOI: 10.1111/clr.13386
http://bit.ly/2SxmSXX
Addressing the Need for Clinical Trial End Points in Autosomal Dominant Polycystic Kidney Disease: A Report From the Polycystic Kidney Disease Outcomes Consortium (PKDOC)
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Expansion of multiple cysts throughout both kidneys is thought to lead to progressive loss of kidney function and kidney failure in some patients. In recent years, much has been learned about the pathophysiology of ADPKD. However, to date, only one therapy has been approved in the United States and in other regions for the treatment of ADPKD. Feasible end points and a clear regulatory pathway may stimulate further development in this area and ultimately lead to more treatments for ADPKD successfully reaching the market.
http://bit.ly/2SqJpFH
Acute Kidney Injury Due to Ovarian Hyperstimulation Syndrome
Ovarian hyperstimulation syndrome (OHSS) is a complication of assisted reproductive treatments such as in vitro fertilization (IVF). The pathophysiology of severe OHSS includes a humorally mediated capillary leak syndrome that is predominantly centered on the intra-abdominal space. Severe OHSS is frequently complicated by acute kidney injury (AKI), which can be due to any of a variety of mechanisms, each requiring a different management strategy. Mechanisms of AKI in severe OHSS include intravascular volume depletion, kidney edema due to capillary leak, intra-abdominal hypertension or compartment syndrome, and obstructive uropathy due to ovarian enlargement.
http://bit.ly/2Ag1RK7
Erratum Regarding “Phosphorus Content of Popular Beverages” (Am J Kidney Dis. 2015;65[6]:969-971)
In the Research Letter entitled "Phosphorus Content of Popular Beverages" that appeared in the June 2015 issue of AJKD (Moser et al, volume 65, issue 6, pages 969-971) there was a numerical error in the fourth sentence of the first full paragraph on page 971. The sentence "The absolute difference in phosphorus content between measured and reference values ranged from −8 to +261 mg per 8 fl oz" should have read "The absolute difference in phosphorus content between measured and reference values ranged from −9 to +261 mg per 8 fl oz." This numerical error does not affect the conclusions of the study.
http://bit.ly/2SwAse8
Systematic external evaluation of published population pharmacokinetic models of mycophenolate mofetil in adult kidney transplant recipients co‐administered with tacrolimus
Abstract
AIMS
Various mycophenolate mofetil (MMF) population pharmacokinetic (popPK) models have been developed to describe its PK characteristics and facilitate its optimal dosing in adult kidney transplant recipients co‐administered with tacrolimus. However, the external predictive performance has been unclear. Thus, this study aimed to comprehensively evaluate the external predictability of published MMF popPK models in such populations and investigate the potential influencing factors.
METHODS
The external predictability of qualified popPK models was evaluated using an independent dataset. The evaluation included prediction‐ and simulation‐based diagnostics, and Bayesian forecasting. In addition, factors influencing model predictability, especially the impact of structural models, were investigated.
RESULTS
Fifty full PK profiles of 45 patients were included in the evaluation dataset and 11 published popPK models were identified and evaluated. In prediction‐based diagnostics, the prediction error within ±30% was less than 50% in most published models. The prediction‐ and variability‐corrected visual predictive check and posterior predictive check showed large discrepancies between the observations and simulations in most models. Moreover, the normalized prediction distribution errors of all models did not follow a normal distribution. Bayesian forecasting demonstrated an improvement of the model predictability. Furthermore, the predictive performance of two‐compartment (2CMT) models incorporating the enterohepatic circulation (EHC) process was not superior to that of conventional 2CMT models.
CONCLUSIONS
The published models showed large variability and unsatisfactory predictive performance, which indicated that therapeutic drug monitoring was necessary for MMF clinical application. Further studies incorporating potential covariates need to be conducted to investigate the key factors influencing model predictability of MMF.
http://bit.ly/2EYKS2I
CC Nerd-The Case of the Unknown Quantity
Lung-protective ventilation is often considered a simple truth when managing critical care patients on mechanical ventilation. Despite this sense of certainty, the knowledge of exactly how and when to perform such ventilatory strategies is incomplete. The recently published PReVENT adds yet more uncertainty to the true efficacy of low tidal volume ventilation in patients without […]
EMCrit Project by Rory Spiegel.
http://bit.ly/2Sr0AHf
In vivo long-term investigation of tumor bearing mKate2 by an in-house fluorescence molecular imaging system
Optical imaging is one of the most common, low-cost imaging tools used for investigating the tumor biological behavior in vivo. This study explores the feasibility and sensitivity of a near infrared fluorescen...
http://bit.ly/2EV4ODV
Preparation, Procedures and Evaluation of Platelet-Rich Plasma Injection in the Treatment of Knee Osteoarthritis
Knee osteoarthritis is frequently seen in the orthopedic department. We introduce in detail the entire knee osteoarthritis treatment process with platelet-rich plasma injection, including preparation, procedures, and evaluation.
http://bit.ly/2ESjeUq
PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome
Abstract
Background
Chronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.
Objective
We analyzed hotspot PIK3CA gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of PIK3CA mutations with patients' clinical and pathological features.
Methods
The study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.
Results
PIK3CA mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, PIK3CA mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between PIK3CA mutations and patients' clinical features or TP53 mutation profile.
Conclusion
This is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.
http://bit.ly/2AfzuvB
Association of HLA-G 3′ UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections
Abstract
Background
Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients.
Methods
We investigated the influence of the HLA-G 14 bp In/Del (rs66554220) and + 3142C/G (rs1063320) polymorphisms in 130 cases of HPV16 infection, 130 cases of HPV18 infection and 185 age-matched, unrelated, HPV-negative, and cytologically normal Chinese Han women. Case-matched cervical biopsy tissues were evaluated by immunohistochemistry.
Results
Our findings show that the frequency of alleles, 14 bp In (38.5% vs 29.2%, OR = 1.52, P < 0.05) and + 3142G (72.7% vs 57.0%, OR = 2.01, P < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The HLA-G polymorphisms (alleles 14 bp In and + 3142G) are also associated with the progression of HPV18-related cervical lesions. Moreover, HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in patients with adenocarcinoma; however, a significant association between these characteristics and the HLA-G polymorphisms was not observed.
Conclusion
Our results support that the HLA-G 14 bp In and + 3142G alleles are risk factors for HPV18 infections and influence the progression of HPV18-related cervical lesions. This suggests that HLA-G-driven immune mechanisms play an important role in cervical carcinogenesis.
http://bit.ly/2SptsQ4
Implications of reconstruction protocol for histo-biological characterisation of breast cancers using FDG-PET radiomics
Abstract
Background
The aim of this study is to determine if the choice of the 18F-FDG-PET protocol, especially matrix size and reconstruction algorithm, is of importance to discriminate between immunohistochemical subtypes (luminal versus non-luminal) in breast cancer with textural features (TFs).
Procedures
Forty-seven patients referred for breast cancer staging in the framework of a prospective study were reviewed as part of an ancillary study. In addition to standard PET imaging (PSFWholeBody), a high-resolution breast acquisition was performed and reconstructed with OSEM and PSF (OSEMbreast/PSFbreast). PET standard metrics and TFs were extracted. For each reconstruction protocol, a prediction model for tumour classification was built using a random forests method. Spearman coefficients were used to seek correlation between PET metrics.
Results
PSFWholeBody showed lower numbers of voxels within VOIs than OSEMbreast and PSFbreast with median (interquartile range) equal to 130 (43–271), 316 (167–1042), 367 (107–1221), respectively (p < 0.0001). Therefore, using LifeX software, 28 (59%), 46 (98%) and 42 (89%) patients were exploitable with PSFWholeBody, OSEMbreast and PSFbreast, respectively.
On matched comparisons, PSFbreast reconstruction presented better abilities than PSFwholeBody and OSEMbreast for the classification of luminal versus non-luminal breast tumours with an accuracy reaching 85.7% as compared to 67.8% for PSFwholeBody and 73.8% for OSEMbreast. PSFbreast accuracy, sensitivity, specificity, PPV and NPV were equal to 85.7%, 94.3%, 42.9%, 89.2%, 60.0%, respectively. Coarseness and ZLNU were found to be main variables of importance, appearing in all three prediction models. Coarseness was correlated with SUVmax on PSFwholeBody images (ρ = − 0.526, p = 0.005), whereas it was not on OSEMbreast (ρ = − 0.183, p = 0.244) and PSFbreast (ρ = − 0.244, p = 0.119) images. Moreover, the range of its values was higher on PSFbreast images as compared to OSEMbreast, especially in small lesions (MTV < 3 ml).
Conclusions
High-resolution breast PET acquisitions, applying both small-voxel matrix and PSF modelling, appeared to improve the characterisation of breast tumours.
http://bit.ly/2RoAA1I
Adipose stem cell crosstalk with chemo-residual breast cancer cells: implications for tumor recurrence
Abstract
Purpose
Most triple-negative breast cancer (TNBC) patients exhibit an incomplete response to neoadjuvant chemotherapy, resulting in chemo-residual tumor cells that drive tumor recurrence and patient mortality. Accordingly, strategies for eliminating chemo-residual tumor cells are urgently needed. Although stromal cells contribute to tumor cell invasion, to date, their ability to influence chemo-residual tumor cell behavior has not been examined. Our study is the first to investigate cross-talk between adipose-derived stem cells (ASCs) and chemo-residual TNBC cells. We examine if ASCs promote chemo-residual tumor cell proliferation, having implications for tumor recurrence.
Methods
ASC migration toward chemo-residual TNBC cells was tested in a transwell migration assay. Importance of the SDF-1α/CXCR4 axis was determined using neutralizing antibodies and a small molecule inhibitor. The ability of ASCs to drive tumor cell proliferation was analyzed by culturing tumor cells ± ASC conditioned media (CM) and determining cell counts. Downstream signaling pathways activated in chemo-residual tumor cells following their exposure to ASC CM were studied by immunoblotting. Importance of FGF2 in promoting proliferation was assessed using an FGF2-neutralizing antibody.
Results
ASCs migrated toward chemo-residual TNBC cells in a CXCR4/SDF-1α-dependent manner. Moreover, ASC CM increased chemo-residual tumor cell proliferation and activity of extracellular signal-regulated kinase (ERK). An FGF2-neutralizing antibody inhibited ASC-induced chemo-residual tumor cell proliferation.
Conclusions
ASCs migrate toward chemo-residual TNBC cells via SDF-1α/CXCR4 signaling, and drive chemo-residual tumor cell proliferation in a paracrine manner by secreting FGF2 and activating ERK. This paracrine signaling can potentially be targeted to prevent tumor recurrence.
http://bit.ly/2So6vg0
Is early postoperative hypoalbuminemia really a risk factor for acute kidney injury after hip fracture surgery?
Publication date: Available online 28 December 2018
Source: Injury
Author(s): Rui-Juan Guo, Fu-Shan Xue, Liu-Jia-Zi Shao, Zheng Li
http://bit.ly/2EYdiKz
Regarding reverse total shoulder arhroplasty for the treatment of failed fixation in proximal humeral fractures
Publication date: Available online 28 December 2018
Source: Injury
Author(s): Katie Hughes, Simon Bellringer, Gareth Chan, Laurence Dodd, Samantha Hook
http://bit.ly/2EVRxdw
Proposal for the classification of peri-implant femoral fractures: Retrospective cohort study
Publication date: Available online 28 December 2018
Source: Injury
Author(s): Ernest Beng Kee Kwek, On behalf of the Singapore Orthopaedic Research CollaborativE (SORCE) Group
http://bit.ly/2EVYmfY
Management of blunt adrenal gland injury in a community-based hospital
Publication date: Available online 28 December 2018
Source: Injury
Author(s): Fathima T. Kunhivalappil, Ashraf F. Hefny, Fikri M. Abu-Zidan
Abstract
Introduction
Injury of the adrenal gland in blunt trauma is rare. The routine usage of the whole body computed tomography (CT) scan helps in early diagnosis. We aimed to study the incidence, mechanism of injury, management, and outcome of adrenal injury in blunt trauma patients treated in a community-based hospital.
Methods
CT scan of the abdomen of all blunt trauma patients who were admitted to our institution between October 2010 and March 2018 were retrospectively reviewed. The files of all the patients with CT scan-detected adrenal injuries were retrieved. Studied variables included demography, mechanism of injury, associated injuries, GCS, ISS, Intensive Care Unit admission, hospital stay, and outcome.
Results
4991 blunt trauma patients were admitted to the hospital. CT scan of the abdomen was performed for 2359 (47%) patients. Blunt adrenal injuries were diagnosed in eleven male patients (0.22 %). The main mechanism of injury was motor vehicle collisions in eight (72.7 %) patients. Nine (81.8 %) patients had right adrenal gland injury. The mean (range) ISS was 22 (6-50). All patients had intra-adrenal hematoma and periadrenal fat stranding. None of our patients had acute adrenal insufficiency. One patient died (overall mortality 9.1%).
Conclusions
The incidence of blunt adrenal injury, although rare, is similar in a community-based hospital to those reported from trauma I centers. It is associated with severe and multiple organ injuries. Blunt adrenal injuries are usually self-limiting.
http://bit.ly/2EU66y2
Surgical approaches for open reduction and internal fixation of intra-articular distal humerus fractures in adults: a systematic review and meta-analysis
Publication date: Available online 28 December 2018
Source: Injury
Author(s): Siddhartha Sharma, Rakesh John, Mandeep S. Dhillon, Kamal Kishore
http://bit.ly/2EUTc3D
Upper GI biopsies for Adenocarcinoma – how many biopsies should endoscopists take?
Abstract
Aims
There is evidence that 4 or 5 gastric cancer biopsies are required for accurate HER2 interpretation. However, the number of biopsies that need to be taken to reach this number of viable cancer biopsies is without evidence. This study aimed to address this gap by assessing the number of biopsies required to get at least 4 viable biopsies containing cancer
Methods and results
105 consecutive biopsy cases of gastric and oesophageal adenocarcinoma were retrieved from file. Only definite cancer diagnoses were included; missed cancers or unproven cases were not considered. The cases were reviewed and the number of biopsies taken, and the number containing viable tumour was recorded. In total, 667 biopsies were taken of which 471 had viable tumour (70.6%) 70/105 cases (67%) had 4 viable tumour biopsies but only 47/105 (45%) had 5 viable tumour biopsies. In order to have a >90% chance of having 4 viable tumour biopsies, 7 biopsies needed to be taken, while 10 or more biopsies were required for a >90% chance of 5 viable tumour biopsies. Mathematically, using a 0.7 probability for a single biopsy, 8 biopsies would be required for a 94% chance of at least 4 viable tumour biopsies.
Conclusion
In our large upper GI cancer centre, many biopsy cases do not contain sufficient material for adequate HER2 assessment. In order to meet the 4 biopsy requirement for adequate HER2 assessment in >90% of cases, at least 8 biopsies need to be taken, while 10 biopsies would be required for the 5 cancer biopsy threshold.
This article is protected by copyright. All rights reserved.
http://bit.ly/2TfM6Kk
Impact of Insulin Tregopil and its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open‐label, Placebo Controlled, Crossover Study
Abstract
Oral insulin tregopil (IN‐105; new drug under development) may be co‐administered with oral anti‐diabetic drugs such as metformin in type 2 diabetes mellitus patients for optimal glycemic control. IN‐105 has sodium caprate excipient, a permeation enhancer, for enhancing absorption in stomach and increasing bioavailability via oral route. Sodium caprate may increase bioavailability of metformin by a similar mechanism. Therefore, it was necessary to study effect of IN‐105 on pharmacokinetics of metformin. In this randomized, open‐label, cross‐over study, metformin was administered to healthy volunteers receiving IN‐105/placebo under fed/fasting conditions. 90% CI of GMR of AUC0‐inf (fasting and fed) and Cmax (fed) of metformin were within 0.80–1.25. Under fasting conditions, upper bound margin of Cmax was just beyond this range (i.e. 1.27) and was concluded as functionally not relevant. There was no clinically significant effect of sodium caprate/IN‐105 on pharmacokinetics of metformin under fasting/fed conditions and it was safe.
This article is protected by copyright. All rights reserved.
http://bit.ly/2s2czPC
The ACCOuNT Consortium: a model for the discovery, translation and implementation of precision medicine in African Americans
Abstract
The majority of pharmacogenomic studies have been conducted on European ancestry populations, thereby excluding minority populations and impeding the discovery and translation of African American specific genetic variation into precision medicine. Without accounting for variants found in African Americans, clinical recommendations based solely on genetic biomarkers found in European populations could result in misclassification of drug response in African Americans patients.
To address these challenges, we formed the Transdisciplinary Collaborative Center (TCC), ACCOuNT (African American Cardiovascular Pharmacogenetic Consortium), to discover novel genetic variants in African Americans related to clinically actionable cardiovascular phenotypes and to incorporate African American‐specific sequence variations into clinical recommendations at the point of care. The TCC consists of two research projects focused on discovery and translation of genetic findings and four cores that support the projects. In addition, the largest repository of pharmacogenomic information on African Americans is being established as well as lasting infrastructure that can be utilized to spur continued research in this understudied population.
This article is protected by copyright. All rights reserved.
http://bit.ly/2LEUQH5
Cancers, Vol. 11, Pages 31: Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge
Cancers, Vol. 11, Pages 31: Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge
Cancers doi: 10.3390/cancers11010031
Authors: Paolo Giuffrida Alessandro Vanoli Giovanni Arpa Arturo Bonometti Ombretta Luinetti Enrico Solcia Gino Roberto Corazza Marco Paulli Antonio Di Sabatino
Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumour-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review, we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.
http://bit.ly/2BLgWDf
Nurse Documentation of Sexual Orientation and Gender Identity in Home Healthcare: A Text Mining Study
http://bit.ly/2Teol5a
Sequencing of Chemotherapy and Radiotherapy for Newly Diagnosed Anaplastic Oligodendroglioma and Oligoastrocytoma
http://bit.ly/2AmQ4K6
Factors Influencing Clinical and Setting Pathways After Discharge From an Acute Palliative/Supportive Care Unit
http://bit.ly/2SrrrCK
A new counterintuitive training for adult amblyopia
Abstract
Objectives
The aim of this study was to investigate whether short‐term inverse occlusion, combined with moderate physical exercise, could promote the recovery of visual acuity and stereopsis in a group of adult anisometropic amblyopes.
Methods
Ten adult anisometropic patients underwent six brief (2 h) training sessions over a period of 4 weeks. Each training session consisted in the occlusion of the amblyopic eye combined with physical exercise (intermittent cycling on a stationary bike). Visual acuity (measured with ETDRS charts), stereoacuity (measured with the TNO test), and sensory eye dominance (measured with binocular rivalry) were tested before and after each training session, as well as in follow‐up visits performed 1 month, 3 months, and 1 year after the end of the training.
Results
After six brief (2 h) training sessions, visual acuity improved in all 10 patients (0.15 ± 0.02 LogMar), and six of them also recovered stereopsis. The improvement was preserved for up to 1 year after training. A pilot experiment suggested that physical activity might play an important role for the recovery of visual acuity and stereopsis.
Conclusions
Our results suggest a noninvasive training strategy for adult human amblyopia based on an inverse‐occlusion procedure combined with physical exercise.
http://bit.ly/2SsMN2W
Post‐marketing dosing changes in the label of biologicals
Aim
To evaluate post‐marketing label changes in dosing information of biologicals.
Methods
Biologicals authorised between 2007 and 2014 by the European Medicines Agency (EMA) were included and followed up from marketing authorisation until 31 December 2016 or date of withdrawal of the marketing authorisation. The primary outcome of the study was defined as label change in dosing information for the initially approved indication. Incidence of changes, type of change and mean time to change were assessed. As a secondary outcome, label changes in dosing information for extended indications were assessed.
Results
A total of 71 biologicals were included. Dosing information in the label changed for the initial indication during follow‐up for eight products (11%). In one of the eight products the change concerned an increase in dose. Also, a change in dosing frequency was identified in three products,for one product a recommendation was added that therapy could be initiated with or without a loading dose, and for one product the minimum dose was removed and a maximum dose was added. For the remaining product the dose was decreased due to safety issues. For 30 products (42%) the indication was extended at least once. No changes in dosing information were observed for the extended indications (n=59) during follow‐up.
Conclusions
This study showed that in 11% of the biologicals the dosing for the initial indication in the label was changed. In contrast to small molecules, the dose was rarely reduced for safety reasons.
http://bit.ly/2Ron527
Prospective randomized controlled clinical trial to compare hard tissue changes following socket preservation using alloplasts, xenografts vs no grafting: Clinical and histological findings
Abstract
Purpose
To compare dimensional changes and bone quality of two different grafting materials used for socket preservation.
Materials and Methods
Thirty‐three patients requiring extraction were recruited and randomly assigned to receive: biphasic calcium sulfate/ hydroxyapatite (BCS/HA); bovine derived xenograft (BDX) or no grafting (Control). Ridge width (at −3 and −6 mm) and vertical distance from a stent were measured at the time of extraction/grafting. Measurements were repeated at reentry and core biopsies were harvested.
Results
Baseline vertical distance for the BDX, C and BCS/HA groups were 7.45 ± 3.1, 7.69 ± 4.2, and 6.75 ± 3.5 mm, respectively (P = .830). Post‐op, C group had greater vertical loss (1.71 ± 0.4 mm) compared to BCS/HA (0.65 ± 0.5) and BDX (0.25 ± 0.2 mm), P = .059. Mean baseline width at −3 mm was 8.69 ± 1.1 mm, 8.31 ± 1.4 mm, and 9.0 ± 1.1 mm, respectively (P = .509). Post‐op, this width was reduced by 2.96 ± 0.3 mm (C), 1.56 ± 0.4 mm (BDX), and 0.5 ± 0.4 mm (BCS/HA), P = .001. Mean ridge width at −6 mm for the C (6.5 ± 1.7 mm) was significantly smaller than BCS/HA (7.95 ± 2.8 mm) and BDX (8.85 ± 1.9 mm), P = .043. Histologically, the BDX group had greater residual scaffold material and less vital bone compared to the BCS/HA group. Pain scores were relatively low for all groups.
Conclusions
BCS/HA may be used for socket preservation with similar or better results compared to BDX. The significance of greater residual scaffold found in the BDX group is yet to be determined.
http://bit.ly/2EVtBGP
On inflammation‐immunological balance theory—A critical apprehension of disease concepts around implants: Mucositis and marginal bone loss may represent normal conditions and not necessarily a state of disease
Abstract
Background
Oral implants have displayed clinical survival results at the 95%‐99% level for over 10 years of follow up. Nevertheless, some clinical researchers see implant disease as a most common phenomenon. Oral implants are regarded to display disease in the form of mucositis or peri‐implantitis. One purpose of the present article is to investigate whether a state of disease is necessarily occurring when implants display soft tissue inflammation or partially lose their bony attachment. Another purpose of this article is to analyze the mode of defense for implants that are placed in a bacteria rich environment and to analyze when an obtained steady state between tissue and the foreign materials is disturbed.
Materials and Methods
The present article is authored as a narrative review contribution.
Results
Evidence is presented that further documents the fact that implants are but foreign bodies that elicit a foreign body response when placed in bone tissue. The foreign body response is characterized by a bony demarcation of implants in combination with a chronic inflammation in soft tissues. Oral implants survive in the bacteria‐rich environments where they are placed due to a dual defense system in form of chronic inflammation coupled to immunological cellular actions. Clear evidence is presented that questions the automatic diagnostics of an oral implant disease based on the finding of so called mucositis that in many instances represents but a normal tissue response to foreign body implants instead of disease. Furthermore, neither is marginal bone loss around implants necessarily indicative of a disease; the challenge to the implant represented by bone resorption may be successfully counteracted by local defense mechanisms and a new tissue‐implant steady state may evolve. Similar reactions including chronic inflammation occur in the interface of orthopedic implants that display similarly good long‐term results as do oral implants, if mainly evaluated based on revision surgery in orthopedic cases. The most common mode of failure of orthopedic implants is aseptic loosening which has been found coupled to a reactivation of the inflammatory‐ immune system.
Conclusions
Implants survive in the body due to balanced defense reactions in form of chronic inflammation and activation of the innate immune system. Ten year results of oral and hip /knee implants are hence in the 90+ percentage region. Clinical problems may occur with bone resorption that in most cases is successfully counterbalanced by the defense/healing systems. However, in certain instances implant failure will ensue characterized by bacterial attacks and/or by reactivation of the immune system that now will act to remove the foreign bodies from the tissues.
http://bit.ly/2EVgIxl
Accuracy of newly developed sleeve‐designed templates for insertion of dental implants: A prospective multicenters clinical trial
Abstract
Background
The insertion of dental implants by means of computer‐assisted template‐based surgery is an established method.
Purpose
To investigate the accuracy of a newly developed sleeve‐designed template and to evaluate differences between maxillary and mandibular implants as well as anterior versus posterior area.
Materials and Methods
Any partially edentulous patients requiring at least one implant to be planned on three‐dimensional cone beam computed tomography scan, according to a computer‐assisted template‐based protocol, were consecutively enrolled at two centers. Any potential implant position was considered eligible for the present trial. Outcome measures were: implant failure, complications, and accuracy.
Results
A total of 39 patients with 119 implants were evaluated. No patients dropped out during the study period (mean follow‐up 12.4 ± 7.1 months). Three implants failed at centre two, whereas, one complication was experienced at centre one (limited access in posterior area). Differences were not statistically significant (P > .05). The mean deviations were 0.53 ± 0.46 mm (range 0.05‐3.38 mm; 95% CI 0.32‐0.48 mm) in the horizontal plan (mesio‐distal); 0.42 ± 0.37 mm (range 0.0‐1.53 mm; 95% CI 0.26‐0.40 mm) in the vertical plan (apico‐coronal); and 1.43 ± 1.98° (range 0.03‐11.8°; 95% CI 0.31‐1.01°) in angle. Differences between centers were compared using the nonparametric Mann‐Whitney U test (P > .05). More accurate results were found for anterior implants in both horizontal plan and angle.
Conclusion
This study showed good precision in all the parameters measured. The results were thus in a range equal to or better than the mean precision found in numerous clinical trials described in the literature. Posterior implants were less accurate because of the use of open sleeves template.
http://bit.ly/2EUKKk3
Primary Sclerosing Cholangitis Risk Estimate Tool (PREsTo) Predicts Outcomes of the Disease: A Derivation and Validation Study Using Machine Learning
Improved methods are needed to risk stratify and predict outcomes in patients with primary sclerosing cholangitis (PSC). Therefore, we sought to derive and validate a prediction model and compare its performance to existing surrogate markers. The model was derived using 509 subjects from a multicenter North American cohort and validated in an international multicenter cohort (n = 278). Gradient boosting, a machine‐based learning technique, was used to create the model. The endpoint was hepatic decompensation (ascites, variceal hemorrhage, or encephalopathy). Subjects with advanced PSC or cholangiocarcinoma (CCA) at baseline were excluded. The PSC risk estimate tool (PREsTo) consists of nine variables: bilirubin, albumin, serum alkaline phosphatase (SAP) times the upper limit of normal (ULN), platelets, aspartate aminotransferase (AST), hemoglobin, sodium, patient age, and number of years since PSC was diagnosed. Validation in an independent cohort confirms that PREsTo accurately predicts decompensation (C‐statistic, 0.90; 95% confidence interval [CI], 0.84‐0.95) and performed well compared to Model for End‐Stage Liver Disease (MELD) score (C‐statistic, 0.72; 95% CI, 0.57‐0.84), Mayo PSC risk score (C‐statistic, 0.85; 95% CI, 0.77‐0.92), and SAP <1.5 × ULN (C‐statistic, 0.65; 95% CI, 0.55‐0.73). PREsTo continued to be accurate among individuals with a bilirubin <2.0 mg/dL (C‐statistic, 0.90; 95% CI, 0.82‐0.96) and when the score was reapplied at a later course in the disease (C‐statistic, 0.82; 95% CI, 0.64‐0.95). Conclusion: PREsTo accurately predicts hepatic decompensation (HD) in PSC and exceeds the performance among other widely available, noninvasive prognostic scoring systems.
http://bit.ly/2LEgwTT
A systematic review of the morphology and function of the sacrotuberous ligament
Introduction
The sacrotuberous ligament (STL) has been linked to conditions such as pelvic girdle pain and pudendal nerve entrapment, yet its contribution to pelvic stability is debated. The purpose of this review was to explore the current understanding of the STL and highlight any gaps in knowledge regarding its anatomy and function.
Materials and Methods
A systematic search of the literature was conducted, focussing on the morphology and attachments of the STL, the relationship of the STL with surrounding structures, and its neurovascular supply and function.
Results
A total of 67 papers and 4 textbooks were obtained. The attachment sites of the STL are largely consistent; however the extent of its connections with the long head of biceps femoris, gluteus maximus, piriformis, the posterior layer of the thoracolumbar fascia, and sacrospinous ligament are unclear. Morphometric parameters, such as STL length (6.4‐9.4 cm), depth (3‐4 cm) and width (1.0‐4.5 cm, at its mid‐point) are variable within and between studies, and little is known about potential side‐, age‐ or sex‐related differences. The STL is pierced in several sites by the inferior and superior gluteal arteries, but information on its innervation pattern is sparse. Functionally the STL may limit sacral nutation but appears to have a limited contribution to pelvic stability.
Conclusion
Some morphological aspects of the STL warrant further investigation, particularly its connections with surrounding structures and innervation pattern, and function. Knowledge of the detailed anatomy and function of this ligament is important to better understanding its role in clinical conditions.
This article is protected by copyright. All rights reserved.
http://bit.ly/2TeQJnG
Revisiting the genital and femoral branches of the genitofemoral nerve: Suggestion for a more accurate terminology
INTRODUCTION
The genitofemoral nerve is a branch of the lumbar plexus originating from the ventral rami of the first and second lumbar spinal nerves. During routine dissections of this nerve, we have occasionally observed that the genital branch of the genitofemoral nerve gave rise to the femoral branch, and the femoral branch of the genitofemoral nerve gave rise to the genital branch. Therefore, this study aimed to investigate the aforementioned distributions of the genitofemoral nerve in a large number of cadaveric specimens.
MATERIALS AND METHODS
Twenty‐four sides from fourteen fresh‐frozen cadavers derived from nine males and five females were used in this study. For proximal branches of the genitofemoral nerve i.e. as they first arise from the genitofemoral nerve, the terms "medial branch" and "lateral branch" were used. For the final distribution, the terms "genital branch" and "femoral branch" were used.
RESULTS
On eight sides (33.3%) with nine branches, one or two branch(s) from either the medial or lateral branch became coursed as the femoral or genital branches (five became femoral and four became genital branches).
CONCLUSIONS
Our study revealed that the distribution of the genitofemoral nerve is more complicated than previously described. The "medial branch" and "lateral branch" that we have used in the present study for describing the proximal branches of the genitofemoral nerve are more practical terms to describe the genitofemoral nerve.
This article is protected by copyright. All rights reserved.
http://bit.ly/2CDot8O
MLH1 enhances the sensitivity of human endometrial carcinoma cells to cisplatin by activating the MLH1/c-Abl apoptosis signaling pathway
Abstract
Background
MLH1 plays a critical role in maintaining the fidelity of DNA replication, and defects in human MLH1 have been reported. However, the role of MLH1 in endometrial carcinoma has not been fully investigated. Therefore, we aimed to study the role of MLH1 in the sensitivity of human endometrial carcinoma cells to cisplatin.
Methods
In this study, we detected the expression of MLH1 in Ishikawa and RL95–2 cells. MLH1-siRNA and ADV-MLH1 were adopted for the silencing and overexpression of MLH1, respectively. Real-time polymerase chain reaction, Western blotting, cell proliferation assays, and cell cycle and apoptotic analyses by flow cytometry were employed to explore the underlying mechanism. A mouse xenograft model was used to investigate the effect of MLH1 on tumor growth after treatment with cisplatin.
Results
Over-expression of MLH1 in Ishikawa cells dramatically increased the sensitivity of cells to cisplatin and enhanced cell apoptosis. By contrast, knockdown of MLH1 yielded the opposite effects in vitro. Mechanistically, cisplatin induced the MLH1/c-Abl apoptosis signaling pathway in ADV-MLH1-infected endometrial carcinoma cells, and these effects involved c-Abl, caspase-9, caspase-3 and PARP. Altogether, our results indicate that ADV-MLH1 might attenuate Ishikawa cell growth in vivo, resulting in increased cisplatin sensitivity.
Conclusions
MLH1 may render endometrial carcinoma cells more sensitive to cisplatin by activating the MLH1/c-Abl apoptosis signaling pathway. In addition, an applicable adenovirus vector (ADV-MLH1) for MLH1 overexpression in endometrial carcinoma was generated. Thus, ADV-MLH1 might be a novel potential therapeutic target for endometrial carcinoma.
http://bit.ly/2EV2VqE
A genome wide SNP genotyping study in the Tunisian population: specific reporting on a subset of common breast cancer risk loci
Abstract
Background
Breast cancer is the most common cancer in women worldwide. Around 50% of breast cancer familial risk has been so far explained by known susceptibility alleles with variable levels of risk and prevalence. The vast majority of these breast cancer associated variations reported to date are from populations of European ancestry. In spite of its heterogeneity and genetic wealth, North-African populations have not been studied by the HapMap and the 1000Genomes projects. Thus, very little is known about the genetic architecture of these populations.
Methods
This study aimed to investigate a subset of common breast cancer loci in the general Tunisian population and to compare their genetic composition to those of other ethnic groups. We undertook a genome-wide haplotype study by genotyping 135 Tunisian subjects using the Affymetrix 6.0-Array. We compared Tunisian allele frequencies and linkage disequilibrium patterns to those of HapMap populations and we performed a comprehensive assessment of the functional effects of several selected variants.
Results
Haplotype analyses showed that at risk haplotypes on 2p24, 4q21, 6q25, 9q31, 10q26, 11p15, 11q13 and 14q32 loci are considerably frequent in the Tunisian population (> 20%). Allele frequency comparison showed that the frequency of rs13329835 is significantly different between Tunisian and all other HapMap populations. LD-blocks and Principle Component Analysis revealed that the genetic characteristics of breast cancer variants in the Tunisian, and so probably the North-African populations, are more similar to those of Europeans than Africans.
Using eQTl analysis, we characterized rs9911630 as the most strongly expression-associated SNP that seems to affect the expression levels of BRCA1 and two long non coding RNAs (NBR2 and LINC008854). Additional in-silico analysis also suggested a potential functional significance of this variant.
Conclusions
We illustrated the utility of combining haplotype analysis in diverse ethnic groups with functional analysis to explore breast cancer genetic architecture in Tunisia. Results presented in this study provide the first report on a large number of common breast cancer genetic polymorphisms in the Tunisian population which may establish a baseline database to guide future association studies in North Africa.
http://bit.ly/2EWSiTD
Diagnostic utility of immunohistochemical analysis and Epstein–Barr virus‐encoded small RNAs in situ hybridisation of cell block sections obtained using fine‐needle aspiration in nasopharyngeal carcinoma with lymph node metastasis
Objective
This study aimed to investigate the diagnostic utility of immunohistochemistry (IHC) analysis (FNA) and Epstein–Barr virus‐ (EBV) encoded small RNAs (EBERs) in situ hybridisation analyses of cell block (CB) sections obtained using fine needle aspiration in nasopharyngeal carcinoma (NPC) with lymph node metastasis.
Methods
A total of 38 FNA biopsies were collected using a Youyi aspirator. The cytomorphology, CB‐based histomorphology, IHC, and EBERs in situ hybridisation were observed and the sensitivity/final diagnostic rates were compared with those of simple smears and a combination of smears and CBs.
Results
The 38 cases of metastatic lymph nodes from NPC displayed the morphological characteristics of non‐keratinising carcinoma in cell smears and CB sections. The tumour cells showed high expression of CK5/6, P63, Ki‐67, and EBERs (94.7%, 36/38 cases) in the CB sections. The sensitivity and the final diagnostic rates were lowest with the simple cell smears (86.8%, 33/38 and 71.1%, 27/38 cases), moderate with the smears combined with CB sections (92.1%, 35/38 cases and 81.6%, 31/38 cases), and the highest with IHC and EBERs in situ hybridisation (94.7%, 36/38 and 94.7%, 36/38 cases).
Conclusions
FNA has great value in the diagnosis of NPC with lymph node metastases, and using cell smears combined with IHC and EBERs in situ hybridisation of CB sections could help clinical doctors promptly identify the primary lesions.
http://bit.ly/2EUnDXF
Role of fine‐needle aspiration in post liver transplant patients: A clinical/cytological review
Background
Fine‐needle aspiration (FNA) of superficial and deep‐seated lesions has been used with high sensitivity and specificity in the diagnosis of neoplastic and nonneoplastic lesions. However, literature of FNA in posttransplant patients is sparse, especially in postliver transplant. We undertook a retrospective study to evaluate the utility of FNA in the clinical management of post liver transplant patients.
Methods
We searched our institution's surgical/cytologic databases (November1993–February2016) to identify liver transplant cases and FNA procedures performed on allograft liver recipients. Institutional IRB approval was obtained for this study.
Results
886 liver allograft recipients were reviewed, 41(5%) of which were transplanted for hepatocellular carcinoma. 62/886(7%) underwent an FNA procedure. 39males and 23females included with mean age of 58years. Mean time between transplant and FNA was 34months.
21/62(34%) were malignant neoplasms, most common malignancy was adenocarcinoma: 8cases(3lung,3pancreas,1colon,1cholangiocarcinoma)and 8cases of transplanted hepatocellular carcinoma patients had recurrence, 6 in the allograft liver and 1case each of metastasis to the iliac bone and periportal lymph node. 3cases were squamous‐cell carcinoma (2lung and 1scalp). 2cases were posttransplant lymphoproliferative disorders.
34/62(55%) cases were benign aspirates from various organs (8lung,6liver,5pancreas,4breast,3thyroid,3lymph‐nodes and 1case each of salivary gland, bile‐duct,intraabdominal,abdominal wall,and oral cavity) 0.6/62(10%) cases were inflammatory.
22cases had histologic correlation: 5true‐positives,16true‐negatives,1false‐negative (a patient with parotid mucoepidermoid carcinoma whose FNA diagnosis was sialadenitis), and no false‐positive. The sensitivity was 83% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 94%.
Conclusions
This review shows that 40/62(65%) of the aspirates were benign lesions, indicating that a conservative approach is recommended in the clinical management of these patients, especially since the interval between transplant and FNA was on average 34months. FNA is a safe, minimally invasive method to follow‐up these patients.
http://bit.ly/2EVC1hM
Atypical Asphysia
Forensic investigation of atypical asphysia
Zhe Cao1, Zhiyuan An2, Xiaoning Hou1, Dong Zhao3
1 Anshan Public Security Bureau, Anshan, China
2 Key Laboratory of Evidence Science (China University of Political Science and Law), Ministry of Education, China, Collaborative Innovation Center of Judicial Civilization, China
3 Key Laboratory of Evidence Science (China University of Political Science and Law), Ministry of Education, China, Collaborative Innovation Center of Judicial Civilization; Key Laboratory of Forensic Genetics of Ministry of Public Security, Institute of Forensic Science, Ministry of Public Security, Beijing, China
Correspondence Address:
Dr. Dong Zhao
25 Xitucheng Road, Haidian, Beijing 100088
China
| Abstract |
Smothering, choking, confined spaces, traumatic asphyxia, positional asphyxia, and other kinds of atypical mechanical asphyxia are not rare in forensic practice. However, these are not commonly well demonstrated in forensic monographs worldwide. The authors researched related works and literatures and summarized these with a view to contribute to the existing teaching resources and provide help to forensic practitioners who are involved in scene investigation and identification of such deaths.
Keywords: Asphyxia, forensic pathology, forensic medicine
| Introduction |  |
Death caused by compression of the neck, such as from hanging, strangling, or throttling, is termed "mechanical asphyxia" and usually has obvious physical findings. However, asphyxias that result from no direct pressure on the neck vessels or trachea, lack typical morphological changes, or result in minimal damage are called "subtle asphyxias"[1] or "atypical mechanical asphyxias," used in this article. Atypical mechanical asphyxias include smothering, choking, environmental hypoxia, traumatic asphyxia, and positional asphyxia, among others.
| Smothering | |
Smothering is a form of asphyxia death caused by obstructing the mouth and nose with hands, airtight papers, soft textiles, or the weight of one's own head.[2]
Smothering can be seen in homicidal or suicidal cases. Homicidal smothering is common in infants, older adults, and people who are unconscious or have restricted motion due to fabric bundling, disease, poisoning, or intoxication. Homicidal smothering can also result when there are significant physical power differences between a perpetrator and victim.[3],[4],[5] Suicidal smothering is common in psychiatric patients; an example includes wrapping tape around one's mouth, nose, or the entire face.[6] Smothering can also occur accidentally. For example, adults who are unconscious or paralyzed because of drunkenness, epilepsy, drug overdose, or having another disease might accidentally asphyxiate themselves. Similarly, for an infant lying face down on an airtight mattress or pillow, the weight of the infant's head might obstruct, distort, and occlude his or her mouth and nose, leading to suffocation. In a third example, sleeping infants with clothes or bedding covering their faces are at an increased risk of suffocation.[1],[2]
In general, it is difficult to identify a case of smothering during forensic scene examination because physical findings are nonspecific.[7],[8] If smothering is suspected, there may be local signs of pressure on the face.[2],[3] In adults, with even slight resistance, signs include skin exfoliation from fingernails; contusions on the nose, cheeks, or chin from fingers; bleeding and skin tears corresponding to the teeth in the oral mucosa; and intramuscular bleeding at the mandibular margin. Nasal deformation is also considered a sign of smothering, but can be caused by emergency tracheal intubation.[3],[5],[7] In infants and adults who are unable to physically resist during asphyxiation, physical damage is difficult to detect.[3] Of note, a body in the prone position concentrates pressure on the face, preventing accumulation of blood into the compressed skin around the mouth and nose, leading to the formation of distinct pale areas caused by the absence of pooled blood. It is, therefore, important not to assume that pale areas such as these have resulted from indentation by smothering.[2]
Without positive physical findings in smothering cases, scene investigation plays a decisive role. Pillows and bedding should be examined for blood or lipstick.[5],[9] For suspected cases of smothering, even if postmortem changes are obvious, suspicious skin lesions should be biopsied for histological examination.[5] In cases of smothering by textiles, the mouth, nasal cavity, and airways should be examined for inhaled fabric fibers. Fibers in the trachea indicate that a patient may have been alive during smothering.[8]
Gagging generally involves placing fabric in a victim's mouth to prevent yelling; the fabric gradually becomes soaked with saliva, and if airtight, will lead to suffocation. Another form of gagging involves placing tape over the mouth or nose, which results in trapped mucus production that eventually leads to suffocation. Obstruction of the nasopharynx by objects in the oral cavity may also lead to gagging and subsequent death.[2] Usually, suspected gagging is confirmed when blocking objects are found, not by any specific physical signs of asphyxia.[3]
| Choking | |
Choking refers to upper respiratory tract blockage by a foreign body leading to suffocation. The foreign body is usually lodged between the larynx and trachea.[10],[11] Death may result from simple hypoxia; however, many deaths occur quickly before the onset of hypoxia. Studies have found that, even in cases in which the airway is not completely blocked, death often occurs, likely from neurogenic-induced cardiac arrest.[2],[9],[11],[12]
Choking is almost always accidental, with cases of homicide and suicide relatively rare.[1],[11] For infants, accidental choking most often occurs with foreign body ingestion; for adults, choking most often occurs with food.[1],[11] Victims in homicidal choking cases are most likely to be older adults, infants, young children, people who are unconscious, or persons debilitated by illness or intoxication. Suicidal choking most often occurs in patients with psychosis or prisoners in jail.[1]
Evidence of coughing helps eliminate choking as a cause of death because it signifies that the respiratory tract was open during upper respiratory blockage.[3] Computed tomography imaging can provide information before an autopsy on the location of a foreign body and can help inform an autopsy plan.[13] Few physical findings are generally seen in choking deaths, so the discovery of a foreign body in the airway, a detailed clinical history, descriptions of the death environment and any resuscitation attempts, and exclusion of other causes of death are critical when forming a conclusion.[1],[9],[11],[12] If the foreign body shifts during resuscitation or otherwise is moved, clinical history might be the only evidence.[3],[13]
Foreign bodies blocking the airway leading to choking generally belong to the following categories.[2]
Foreign objects
Attackers may put a towel or sock into the victim's mouth to prevent shouting; this can cause choking and gagging.[3] In another example, people may inhale sand, piles of gravel, or piles of soil when they fall on them, causing respiratory blockage and resulting in choking death. This scenario may occur accidentally at a construction site, during a traffic accident, or in children playing in or eating sand.[3],[14]
Acute obstruction
Acute allergy, steam stimulation, heat inhalation, and acute inflammation may cause swelling of the throat organs, including the epiglottis, tonsils, or glottis, leading to choking. Trauma in the anterior or lateral cervical neck structures can also result in severe swelling of the respiratory tract from bleeding and edema.[1],[2],[7] Tumors, polyps, or cysts can also block respiration, leading to choking.[1],[10],[11]
Foods
The most common foreign bodies causing choking death in adults are foods.[10] Susceptible factors include old age, neuromuscular disease, poor dentition leading to chewing problems, consumption of alcohol or other central nervous system depressants weakening the gag reflex, or other neurological or mental illness (of which poor dentition is an important risk factor).[1],[11],[12],[13] Of patients with mental illness, those with schizophrenia are most likely to choke on food, possibly from a propensity to swallow incompletely chewed food.[11] The majority of adult choking cases occur at patients' homes, nursing homes, or mental hospitals, and often take place suddenly during meals.[1]
When a sudden death occurs while eating or soon after, the possibility of choking must be considered. A search for a blocked airway should be initiated, but in addition, the investigator should also consider factors that could have aggravated the choking episode. Therefore, quality and number of teeth, food debris in the esophagus – which can cause tracheal obstruction from the external oppression – and exclusion of neurological diseases and intoxication are all important when evaluating sudden death during a meal.[1],[9],[11],[12]
It is typical for gastric contents to be present in the throat, trachea, and bronchi after death, caused by reflux or shifting of contents. This is a common postmortem phenomenon, found in 20%–25% of routine examinations. As a result, if a small amount of gastric content is found in the respiratory tract, this does not mean that choking had occurred; however, if the throat or airway is completely blocked by gastric contents, choking can be concluded.[2],[3],[13] The inhalation of gastric contents is more common in people who are unconscious.[1]Importantly, there is no reliable way to distinguish natural food reflux early in the dying process from true inhalation while alive, unless the inhalation occurred during a clinical procedure or another person witnessed the event. In most cases, in the absence of hard evidence, it is unreasonable for forensic officers to conclude that the inhalation of gastric contents is secondary to choking death.[2]
| Environmental Hypoxia | |
Environmental asphyxiation is usually caused by a lack of oxygen in the local environment,[1],[2],[3] and is almost always accidental. Oxygen deficiency can occur secondary to breathing exercises, microbial consumption, activities related to industrial work (such as welding), environmental chemical reactions (such as rust), absorption by chemical substances (such as activated carbon), and presence of toxic gases (such as propane, nitrogen, and methane).[1],[2],[3] An atmospheric oxygen concentration below 5%–10% will cause death in a few minutes, and a concentration of carbon dioxide higher than 10% is lethal.[1] In some cases, death occurs before the onset of hypoxia, and is secondary to overexcitement of the body's chemical sensing system, which causes parasympathetic nervous system-mediated cardiac arrest.[2]
In hypoxia-asphyxia deaths caused by low atmospheric oxygen levels, physical findings are usually absent,[2] making elucidation of the specific cause of death difficult. Investigators must carefully analyze the environment and exclude other causes of death to conclude environmental hypoxia-asphyxia.[3] Measurements of toxic gases and oxygen concentrations in the air, as well as postmortem analysis of blood and tissues, should be performed; in addition, scene simulations may be required.[1]
As a type of environmental hypoxia-asphyxia, plastic bag suffocation is often used as a suicide technique in Western countries. This method is common in young men and elderly women.[15] Some people even use the propane, ether, or helium gas along with the plastic bag. Plastic bag suffocation deaths can also occur accidentally or unexpectedly, such as during sexual asphyxia, children playing with plastic bags, and other occurrences.[1] It is very rare for the use of plastic bags to result in death; however, it is more likely in cases in which the victim is unconscious, or when there is a large difference in strength between the perpetrator and victim.[16]
Plastic bag suffocation often occurs rapidly with few physical signs;[1],[2] however, in a small number of cases, marks on the neck are present corresponding to the areas of bag bundling (such as from a rubber band), or there may be signs of prior injury, such as wrist cutting or abuse.[1],[2] It is a common misconception that the postmortem presence of moisture in the plastic bag confirms that the bag was placed on a breathing human; water droplets form as gas evaporates from the skin, nose, and mouth even if the person was previously deceased.[2]
Because there are usually no specific physical findings, it is difficult to identify cases of plastic bag suffocation unless the bag is over the head at the time of scene investigation or autopsy.[2] If the plastic bag is removed before forensic workers see the corpse, they will not be able to determine the cause of death through forensic examination, and may even conclude that a natural death occurred. Therefore, to identify such cases, forensic workers must pay careful attention during scene exploration and investigation.[1],[3],[9],[16] If necessary, forensic workers can conduct simulations under close monitoring in a protected environment, which can help to pinpoint a cause of death through analysis of time measurements.[4],[6],[17] Specimens collected from the blood, lungs, liver, or other organs for poison analysis should be extracted and stored in a sealed empty bottle along with a plastic bag,[2],[7],[16] frozen, and delivered promptly.[1]
| Traumatic Asphyxia | |
Traumatic asphyxia refers to the compression of the chest or abdomen by massive mechanical forces resulting in thoracic fixation – expansion of thoracic and lower phrenic muscles – leading to respiratory disturbance and death by asphyxiation.[2]
Traumatic asphyxia is common in the following types of accidents: motor vehicle compression or extrusion during traffic accidents; pinning from building collapse, falling rocks, or other objects; trampling by a crowd; compression while standing in a crowded population from sudden external forces; compression by fallen tools or furniture; and compression of infants and children while sleeping with parents (overlaying asphyxia).[1],[2],[18] There are also reports of homicide resulting from a perpetrator kneeling or sitting on the chest of a victim.[19]
The pathological features of traumatic asphyxia are usually quite specific. These include prominent facial and nuchal hyperemia and swelling; numerous petechial hemorrhages on the face or conjunctiva; subconjunctival hemorrhage and edema; and nasal bleeding. In general, a person who dies from traumatic asphyxiation often appears strangled with features extending down to the neck, with no signs of local damage.[2],[20],[21]
However, physical features such as these are not always visible. Studies have shown that, in up to 10% of cases, no petechial hemorrhages are seen on the face or conjunctiva. The reason for this is unclear, but may be related to rapidness of death, lack of obvious chest compression or vagus nerve stimulation, lack of occlusion of the epiglottis, or concurrence of both left heart and right heart impairment at the time of chest compression.[1],[18],[20],[21] On gross examination, lungs may have a purplish red color, congestion, or subserous bleeding with or without obvious expansion of the right heart or superior vena cava; sometimes, there is no evidence of trauma despite severe direct external compression on the chest and abdomen.[1],[2],[3],[9]
Traumatic asphyxia is a diagnosis of exclusion. In addition to supporting evidence from a scene investigation, suffocation death should only be considered after excluding fatal injuries and poisoning.[1],[9],[21]
Overlaying asphyxia is a special form of traumatic asphyxia, often secondary to nasal compression. Physical examination findings are usually absent, so overlaying can be difficult to determine unless the same-bed sleeper admits to crushing the infant or child. Overlaying asphyxia is sometimes attributed to sudden infant death syndrome, so it is important to examine adults' and children's clothes and bedding carefully as well as the scene.[1],[3],[22]
| Positional Asphyxia | |
Positional asphyxia refers occurrences in which respiration is compromised from splinting of the chest or diaphragm preventing normal respiration, or occlusion of the upper airway due to abnormal positioning of the body.[23] Positional asphyxia is almost always an accident, during which the victim cannot extract himself or herself from a specific position or small space. The victim may be further impaired by alcohol or drug intoxication, weakness, neurological disease, or fabric bundling. Common examples of positional asphyxia include limbs tied behind the back while in a prone position (may be performed for restraint by police or psychiatrists for suspects or patients); head-down position (inversion of the body, or head hanging down off the edge of a bathtub); jack-knife position (upper body significantly curved from the waist down); bundled thoracic or abdominal horizontal sling (e.g., a young girl wearing a belt hanging by the abdomen on a swing); excessive flexion or extension of the neck (e.g., during a motor vehicle accident); lack of chest wall expansion in a restricted space (wedging); and a person sandwiched between the wall and the mattress after falling off the bed.[1],[2],[3],[4],[5],[6],[7],[24] A typical case of postural asphyxia involves a drunken person who collapses into a narrow space, excessively distorting the neck and hindering breathing, leading to death.[9]
Cause of death from positional asphyxia often results from reverse suspension of the body such that the movement of the chest wall is restricted by intra-abdominal organs compressing the diaphragm. This prolongs inspiration, and eventually results in respiratory muscle fatigue, leading to slowed movement of the chest wall and subsequent hypoxia. Venous return is effectively limited, and blood flow to the brain is shifted, decreasing blood flow and further aggravating respiratory muscle fatigue; eventually, the heart stops.[1] Positional asphyxia does not require reversal of the entire body; fatal asphyxia may result from the reversal of torso position, excessive flexion of the neck, or pressure on one's face, such as in an intoxicated person whose face is pressed to the floor.[25] The difference between traumatic asphyxia and positional asphyxia is whether the chest and abdomen are compressed by external forces. If chest compression is from an external source, he or she should have been died from traumatic asphyxia. If a deceased person is found in a specific position or restricted space that limits chest activity, the person should have been died from positional asphyxia.[1],[23]
Positional asphyxia can be identified by the following criteria: The body position is consistent with restricted or disordered respiration; scene investigation or historical investigation identifies that an accident had occurred; the deceased person cannot change his or her position for some reason; and other obvious natural or violent causes of death are excluded. A diagnosis of accidental positional asphyxia mainly depends on the evidence obtained from the scene environment.[24],[25] Some forensic investigators believe that, if another disease is present, then either the cause of death is not associated with positional asphyxia, or the onset of the disease makes the deceased patient prone to positional asphyxia.[23] It should be noted that alcohol consumed by a patient with positional asphyxia may be metabolized. Thus, even if the concentration of alcohol in the blood or urine is very low or negative, the possibility of positional asphyxia cannot be ignored.[24]
Wedging is a special form of positional asphyxia, commonly seen in infants and young children whose body or head are compressed in a narrow space. The chest wall is fixed, resulting in airway obstruction that results in asphyxia. Wedging usually occurs between a mattress and wall or mattress and furniture or baby crib. It is most common in infants aged 3–6 months, intoxicated adults, or comatose patients who accidentally fall between a mattress and wall, leading to death. Physical findings of wedging are usually absent.[1],[22]
Acknowledgments
This study was supported by the Open Project of Key Laboratory of Forensic Genetics, Ministry of Public Security (2017FGKFKT05), Program for Young Innovative Research Team from China University of Political Science and Law (2016CXTD05), and Project of Interdisciplinary Science Construction-Forensic Psychology from China University of Political Science and Law.
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