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Head & Neck Jun 2024Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes...
BACKGROUND
Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population.
METHODS
Retrospective multi-institutional review of FF reconstruction for midface ORN (2005-2022; n = 54).
RESULTS
The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02).
CONCLUSION
In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.
PubMed: 38845552
DOI: 10.1002/hed.27824 -
Heart Failure Clinics Jul 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is a relatively prevalent cause of morbidity and mortality. Over the recent years, development of disease-modifying... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a relatively prevalent cause of morbidity and mortality. Over the recent years, development of disease-modifying treatments has enabled stabilization of the circulating transthyretin tetramer and suppression of its hepatic production, resulting in a remarkable improvement in survival of patients with ATTR-CM. Second-generation drugs for silencing are currently under investigation in randomized clinical trials. In vivo gene editing of transthyretin has been achieving unanticipated suppression of hepatic production in ATTR-CM. Trials of antibodies inducing the active removal of transthyretin amyloid deposits in the heart are ongoing, and evidence has gathered for exceptional spontaneous regression of ATTR-CM.
Topics: Humans; Amyloid Neuropathies, Familial; Cardiomyopathies; Benzoxazoles; Prealbumin
PubMed: 38844305
DOI: 10.1016/j.hfc.2024.03.005 -
Heart Failure Clinics Jul 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by the myocardial extracellular deposition of amyloid fibrils formed from the dissociation of TTR tetramer into... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by the myocardial extracellular deposition of amyloid fibrils formed from the dissociation of TTR tetramer into monomers. The rate-limiting step in TTR amyloidogenesis is the dissociation of the TTR tetramer into monomers: Tafamidis is an effective TTR-stabilizer in its native homotetrameric structure. Tafamidis is a safe and effective drug in reducing symptoms, hospitalization and mortality in accurately selected patients affected by hereditary and wild-type transthyretin amyloid cardiomyopathy.
Topics: Humans; Benzoxazoles; Amyloid Neuropathies, Familial; Cardiomyopathies; Prealbumin
PubMed: 38844304
DOI: 10.1016/j.hfc.2024.03.007 -
Heart Failure Clinics Jul 2024Hereditary transthyretin-related amyloidosis (hATTR) is the most common form of familial amyloidosis. It is an autosomal dominant disease caused by a pathogenic variant... (Review)
Review
Hereditary transthyretin-related amyloidosis (hATTR) is the most common form of familial amyloidosis. It is an autosomal dominant disease caused by a pathogenic variant in the TTR gene. More than 140 TTR gene variants have been associated with hATTR, with the Val30Met variant representing the most common worldwide. The clinical phenotype varies according to the gene variant and includes predominantly cardiac, predominantly neurologic, and mixed phenotypes. The present review aims to describe the genotype-phenotype correlations in hATTR. Understanding these correlations is crucial to facilitate the early identification of the disease, predict adverse outcomes, and guide management with approved disease-modifying therapies.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Phenotype; Mutation; Genetic Association Studies; Genotype
PubMed: 38844302
DOI: 10.1016/j.hfc.2024.03.006 -
Heart Failure Clinics Jul 2024Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The... (Review)
Review
Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.
Topics: Humans; Cardiomyopathies; Amyloidosis; Radiopharmaceuticals; Radionuclide Imaging; Bone and Bones; Myocardium; Amyloid Neuropathies, Familial; Heart Failure; Prealbumin
PubMed: 38844301
DOI: 10.1016/j.hfc.2024.03.003 -
PloS One 2024ATTR amyloidosis is caused by deposition of large, insoluble aggregates (amyloid fibrils) of cross-β-sheet TTR protein molecules on the intercellular surfaces of...
ATTR amyloidosis is caused by deposition of large, insoluble aggregates (amyloid fibrils) of cross-β-sheet TTR protein molecules on the intercellular surfaces of tissues. The process of amyloid formation from monomeric TTR protein molecules to amyloid deposits has not been fully characterized and is therefore modeled in this paper. Two models are considered: 1) TTR monomers in the blood spontaneously fold into a β-sheet conformation, aggregate into short proto-fibrils that then circulate in the blood until they find a complementary tissue where the proto-fibrils accumulate to form the large, insoluble amyloid fibrils found in affected tissues. 2) TTR monomers in the native or β-sheet conformation circulate in the blood until they find a tissue binding site and deposit in the tissue or tissues forming amyloid deposits in situ. These models only differ on where the selection for β-sheet complementarity occurs, in the blood where wt-wt, wt-v, and v-v interactions determine selectivity, or on the tissue surface where tissue-wt and tissure-v interactions also determine selectivity. Statistical modeling in both cases thus involves selectivity in fibril aggregation and tissue binding. Because binding of protein molecules into fibrils and binding of fibrils to tissues occurs through multiple weak non-covalent bonds, strong complementarity between β-sheet molecules and between fibrils and tissues is required to explain the insolubility and tissue selectivity of ATTR amyloidosis. Observation of differing tissue selectivity and thence disease phenotypes from either pure wildtype TTR protein or a mix of wildtype and variant molecules in amyloid fibrils evidences the requirement for fibril-tissue complementarity. Understanding the process that forms fibrils and binds fibrils to tissues may lead to new possibilities for interrupting the process and preventing or curing ATTR amyloidosis.
Topics: Prealbumin; Humans; Amyloid; Amyloid Neuropathies, Familial; Amyloidosis; Models, Molecular; Protein Conformation, beta-Strand
PubMed: 38843135
DOI: 10.1371/journal.pone.0304891 -
Obesity Surgery Jul 2024The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not... (Observational Study)
Observational Study
PURPOSE
The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not yet fully understood in pregnant women after BS.
MATERIAL AND METHODS
This single-center retrospective observational cohort study includes all women with a first and single pregnancy after BS who completed at least one clinical and biological nutritional assessment during pregnancy between 2010 and 2016. The quarterly biological assessment comprised blood count, ferritin, calcium, 25OH vitamin D, parathyroid hormone, fasting glucose, albumin, prealbumin, vitamin A, vitamin B12, folic acid, and zinc.
RESULTS
Among 120 pregnancies analysed, two-thirds underwent gastric bypass (Roux-en-Y and one-anastomosis) and one-third a restrictive procedure (adjustable gastric band or sleeve gastrectomy). The median [Q1-Q3] preoperative BMI was 43.8 [41.1-47.7] kg/m and the mean age at pregnancy was 32.6 ± 5.3 years. Weight loss and time from surgery to pregnancy were 35.1 ± 15.4 kg and 2.9 [1.3-4.5] years, respectively. Ten women (8%) gave birth prematurely, and 22 newborns (19%) were SGA. Univariate analysis shows that ferritin was significantly higher in mothers with SGA than in those without SGA (35.5 [22.3-69.5] vs. 15 [10-32] ng/ml) at third trimester of pregnancy. Women who received pre-pregnancy nutritional assessment seemed less likely to give birth to a SGA newborn (32% vs. 54%, p = 0.07).
CONCLUSION
Iron supplementation should be carefully prescribed and closely monitored during pregnancy in women who have undergone BS.
Topics: Humans; Female; Pregnancy; Adult; Retrospective Studies; Ferritins; Pregnancy Outcome; Infant, Newborn; Infant, Small for Gestational Age; Bariatric Surgery; Obesity, Morbid; Birth Weight; Pregnancy Complications
PubMed: 38842761
DOI: 10.1007/s11695-024-07285-3 -
Frontiers in Immunology 2024Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over...
BACKGROUND
Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over decades, gender disparities in sepsis outcomes persist, with research suggesting higher mortality rates in males.
METHODS
This retrospective study aims to delineate gender-specific clinical biomarker profiles impacting sepsis progression and mortality by examining sepsis cases and related clinical data from the past three years. Propensity score matching was used to select age-matched healthy controls for comparison.
RESULTS
Among 265 sepsis patients, a significantly higher proportion were male (60.8%, P<0.001). While mortality did not significantly differ by gender, deceased patients were significantly older (mean 69 vs 43 years, P=0.003), more likely to have hypertension (54% vs 25%, P=0.019), and had higher SOFA scores (mean ~10 vs 4, P<0.01) compared to survivors. Principal Component Analysis (PCA) showed clear separation between sepsis patients and healthy controls. 48 serum biomarkers were significantly altered in sepsis, with Triiodothyronine, Apolipoprotein A, and Serum cystatin C having the highest diagnostic value by ROC analysis. Gender-stratified comparisons identified male-specific (e.g. AFP, HDLC) and female-specific (e.g. Rheumatoid factor, Interleukin-6) diagnostic biomarkers. Deceased patients significantly differed from survivors, with 22 differentially expressed markers; Antithrombin, Prealbumin, HDL cholesterol, Urea nitrogen and Hydroxybutyrate had the highest diagnostic efficiency for mortality.
CONCLUSION
These findings enhance our understanding of gender disparities in sepsis and may guide future therapeutic strategies. Further research is warranted to validate these biomarker profiles and investigate the molecular mechanisms underlying these gender differences in sepsis outcomes.
Topics: Humans; Sepsis; Male; Female; Biomarkers; Aged; Middle Aged; Retrospective Studies; Sex Factors; Adult; Aged, 80 and over
PubMed: 38835774
DOI: 10.3389/fimmu.2024.1413729 -
Environmental Science & Technology Jun 2024Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased...
Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (∼1%) of human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein ffinity urification with ontargeted nalysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants ( dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4'-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed <0.0001%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.
Topics: Prealbumin; Ligands; Humans; Hydrocarbons; Fluorocarbons; Alkanesulfonic Acids; Dust; Sulfonic Acids
PubMed: 38817092
DOI: 10.1021/acs.est.3c10973 -
Digital Health 2024Malnutrition is prevalent among cancer patients, smartphone-based self-administered nutritional assessment tools offer a promising solution for effective nutritional...
Association between nutritional status assessed by a digital self-administered tool (R+ dietitian) and clinicopathologic factors in cancer patients: A comprehensive analysis.
OBJECTIVE
Malnutrition is prevalent among cancer patients, smartphone-based self-administered nutritional assessment tools offer a promising solution for effective nutritional screening. This study aims to retrospectively analyze the relationships between nutritional status evaluated by the digital tool (R+ Dietitian) and clinicopathologic factors of cancer patients.
METHODS
Cancer patients who met the inclusion criteria were divided into two subgroups based on age, Nutritional Risk Screening-2002, Patient-Generated Subjective Global Assessment Short Form, body mass index, and hospital stays for comparison. Correlation and regression analysis were used to comprehensively assess the relationship between nutritional status and clinicopathologic factors.
FINDINGS
A total of 535 hospitalized cancer patients (58.32 ± 11.24 years old) were recruited. Patients identified with nutritional risk assessed by R+ Dietitian were significantly older, had lower body weight, lower body mass index, greater weight loss, and longer hospital stays (all of above, < 0.01). Multiple logistic regression analysis indicated that serum prealbumin concentration (odds ratio: 0.992, 95% confidence interval: 0.987-0.997, = 0.001), weight loss (odds ratio: 7.309, 95% confidence interval: 4.026-13.270, < 0.001), and body mass index < 18.5 (odds ratio: 5.882, 95% confidence interval: 2.695-12.821, < 0.001) predicted nutritional risk indicated by Nutritional Risk Screening-2002 score ≥3. Hemoglobin concentration (odds ratio: 0.983, 95% confidence interval: 0.970-0.996, = 0.011), weight (odds ratio: 1.111, 95% confidence interval: 1.056-1.169, < 0.001), weight loss (odds ratio: 7.502, 95% confidence interval: 4.394-12.810, < 0.001), body mass index (odds ratio: 0.661, 95% confidence interval: 0.564-0.775, < 0.001), and energy intake (odds ratio: 0.996, 95% confidence interval: 0.995-0.997, < 0.001) predicted nutritional risk indicated by Patient-Generated Subjective Global Assessment Short Form score ≥4. Multiple linear regression analysis revealed that Patient-Generated Subjective Global Assessment Short Form scores ≥3 ( = 2.032, = 0.008) were significantly associated with longer hospital stays.
CONCLUSIONS
The nutritional risks assessed by R+ Dietitian accurately reflected the characteristics of malnutrition in cancer patients and predicted hospital stay and cost, indicating the applicability of R+ Dietitian to improving the efficiency of nutritional management for cancer patients.
PubMed: 38812849
DOI: 10.1177/20552076241255475