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The Statistical Fragility of Saline Nasal Irrigation for Rhinosinusitis: A Systematic Review.

OBJECTIVE: To assess the statistical fragility of randomized controlled trials (RCTs) evaluating high-volume saline nasal irrigation (SNI) for rhinosinusitis using fragility analysis. DATA SOURCES: PubMed, MEDLINE, and Embase were searched for RCTs published between May 1976 and January 2026. REVIEW METHODS: This study was reported as per PRISMA guidelines. RCTs that compared high-volume SNI to non-irrigation standard care for acute, recurrent, or chronic rhinosinusitis, and reported ≥ 1 dichotomous outcome, were included. Fragility index (FI), the minimum number of event reversals needed to alter statistical significance, and fragility quotient (FQ), FI normalized to sample size, were calculated for statistically significant dichotomous outcomes. Reverse FI (rFI) and reverse FQ (rFQ) were calculated for non-significant outcomes. RESULTS: Eight RCTs were included, yielding 38 dichotomous outcomes. Eight outcomes (21.1%) were statistically significant. The overall combined median FI was 5 (FQ 0.062), with similar FI values between significant and non-significant outcomes. In over one-fifth of outcomes, loss to follow-up exceeded FI. Analysis of principal dichotomous outcomes from studies demonstrated a median FI of 6 (FQ 0.092), with five of eight (62.5%) outcomes non-significant. CONCLUSION: RCTs evaluating SNI for rhinosinusitis exhibit moderate-to-high statistical fragility, with small outcome changes capable of reversing study conclusions. Because fragility analysis was limited to dichotomous outcomes while many primary endpoints were continuous, our findings should be interpreted as complementary rather than comprehensive appraisals of RCTs. Future RCTs with larger sample sizes, reduced bias, and pre-specified fragility considerations are needed to better define the clinical role of SNI.

Rhinosinusitis

[Lower limb lymphography where there is no lymph circulatory disorder. Normal conditions and their limits (author's transl)].

Further lymphangiography for the lymphatic system dependent on the internal saphenous vein carried out on 70 patients to establish a lymphographical record of the pelvi-abdominal ganglia, simplified the counting of opacified vessels, and assessment of the development of the vascular system and the fragility of the walls and their calibre and pathway. The various aspects were assessed in relation to the anatomical situation (leg, thigh), age group and sex of the patients. Computerised analysis of the information lead to the conclusion that, even under normal conditions, there are statistical differences in the number of opacified vessels in the legs and in vascular fragility of the pre-inguinal region according to age group. The authors discuss the implications of the limits of the normal appearance of the lymphatic vessels.

Adult

[The physiology of sleep and the physiopathology of insomnia].

After a review of the semiology and organization of normal sleep, the neuronal structures presently accepted as participating in sleep mechanisms are discussed. During a series of experiments designed to define the physiopathological role of slow wave sleep in chronic insomnia, we recorded in our laboratory normal subjects of both sexes and insomniacs whose predominant disorders was sleep maintenance. Sleep modifications as a function of aging chiefly involve stage 4, which is reduced by about one half between the ages of 19 and 30. Analyzing a large group of normal and insomniac subjects, it is possible to show a statistical association between very low values of slow wave sleep and short and fragile total sleep. This association cannot be explained simply by an increase in waking pressure. Comparison of a group of 16 insomniacs with 16 age and sex matched normal subjects shows in the insominacs a deficiency of production of slow wave sleep (stages 3 and 4), most probably linked to a disturbed waking/sleep balance, whereas the other parameters of sleep, especially paradoxical stage, remain unmodified. These results are consistent with the hypothesis of a physiopathological role of slow wave sleep deficiency in chronic primary insomnia; on the other hand, slow wave sleep may possibly be responsible for sleep induction and maintenance, playing the role of a physiological hypnogenic mechanism.

Adult

[Computer technology in otospongiosis. 2. Statistics on 15 years of stapedectomy].

To complete their two previous data processing studies on systematization of parameters for otospongiosis and on statistics concerning the otospongiotic disease itself, the authors now develop the study of postoperative functional results obtained over 15 years stapectomies performed according to various techniques. The characteristic of this study is that the functional results are not considered only from the operative technique point of view, but that they also take into account all the factors having an influence upon the functional results, i.e. mechanical operative factors, otospongiotic cochlear factors and, finally the patient's general factor. This work is divided in three parts. The first part considers statistical data drawn from investigating elements taken over a period ranging from 1960 to 1975 from operative findings, surgical techniques and operative complications, particularly during reoperations, i.e., the mechanical part of hearing improvement in otospongiosis surgery. The second part deals with the problem of the medical postoperative care in stapedial surgery and with that of postoperative complications and the therapy used to combat them. It is the study of the cochlear support problem considering both the cochlear fragility facing the operative trauma, and the cochlear deterioration due to the enzymatic action of the otospongiotic microfoci of the lateral wall of the cochlear duct and of the vestibular side of the footplate. The third part is the statistical study made both by means of data processing and of manual investigation, on the long term functional results obtained, on one hand by the surgical solution of the stapedial fixation's mechanical problem, and on the other, by the medical solution of the cochlear problem considered both from the enzymatic and vascular point of view. This study of stapedectomies' long term functional results allows the authors to draw the conclusions which seem to result logically from this very elaborated statistical study concerning near 17000 stapedectomies performed from 1960 through 1975.

Audiometry

[Hemodilution in vitro and parameters of hemostasis].

High molecular weight (approximately 60,000) dextran having been selected in a protocol of per-operative hemodilution, a prior study was undertaken in vitro in order to measure the variations in parameters of hemostasis. Factor of primary hemostasis, of plasma coagulation and fibrinolysis were thus evaluated in control blood samples, not diluted and diluted to 1/5 th by dextran or by a buffer solution. Statistical analysis was carried out using the t-test for pairs of variables. The following emerge from the results: 1 - an absence of difference with regard to the fibrinolytic activity of the plasma, but marked fragility of the fibrin clot in the presence of dextran; 2 - variations for plasma coagulation factors due to dilution; 3 - acceleration of the phase of polymerisation of fibrin monomeres and a decrease in platelet stickiness and aggregation due to dextran.

Blood Coagulation

Ozone and human blood.

Statistically significant changes (P less than .05) were observed in erythrocytes (RBC) and sera of young adult human males following a single short-term exposure to 0.50 ppm ozone (O3) for 2 3/4 hours. The RBC membrane fragility, glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate dehydrogenase (LDH) enzyme activities were increased, while RBC acetylcholinesterase (AcChase) activity and reduced glutathione (GSH) levels were decreased. The RBC glutathione reductase (GSSRase) activities were not significantly altered. Serum GSSRase activity, however, was significantly decreased while serum vitamin E, and lipid peroxidation levels were significantly increased. These alterations tend to disappear gradually, but were still detectable two weeks following exposure.

Acetylcholinesterase

Osmotic fragility of peripheral blood lymphocytes in chronic lymphatic leukemia and malignant lymphoma.

The osmotic fragility (OF) of peripheral blood lymphocytes from patients with chronic lymphatic leukemia (CLL) and non-Hodgkin malignant lymphoma (ML) was investigated employing an automatic recording method and compared with that of lymphocytes from healthy subjects and from patients suffering from various non-neoplastic diseases. The curves from CLL and ML showed a pattern of increased lymphocyte OF compared with those of the two control groups, and the difference was statistically significant ( less than 0.001). In CLL the increase in OF was more pronounced than in ML, and the shape of the curve was different from that in the other groups. The employment of peripheral blood lymphocyte OF as an additional diagnostic parameter in the diagnosis of CLL and ML is suggested.

Adult

Efficacy and safety of Vertebral Body Sliding Osteotomy (VBSO) versus Anterior Cervical Corpectomy and Fusion (ACCF): A systematic review and meta-analysis.

Anterior cervical corpectomy and fusion (ACCF) is an established treatment for complex cervical myelopathy and ossification of the posterior longitudinal ligament (OPLL), yet it carries risks of dural injury and graft-related failure. Vertebral body sliding osteotomy (VBSO) is a novel technique that avoids direct OPLL manipulation by translating the vertebral body anteriorly to enlarge the spinal canal. Although early studies suggest VBSO may reduce complications, evidence remains limited to retrospective cohorts from the technique's developers, with no high-level synthesis directly comparing it to ACCF. We therefore conducted this meta-analysis to compare clinical outcomes, complications, and radiographic parameters between VBSO and ACCF, while critically evaluating the certainty of the evidence and its generalizability. A systematic search of PubMed, Embase, Scopus, the Cochrane Library, and Web of Science (through June 2025) identified four retrospective cohort studies (449 patients; VBSO n&#x2009;=&#x2009;209, ACCF n&#x2009;=&#x2009;240). A critical limitation of the included evidence is that all studies originated from a single institution (Asan Medical Center, Seoul, Korea) with overlapping enrollment periods (2006-2020), increasing the risk of duplicate patient cohorts. Furthermore, the first author (D.-H. Lee) is the same across all included studies, introducing substantial surgeon-expertise bias. Outcomes included neurological recovery, functional outcomes, complications, and radiographic parameters. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Neurological recovery and functional outcomes were comparable between groups. ACCF showed slightly higher postoperative JOA scores (MD -0.59, 95% CI -0.96 to -0.22; p&#x2009;<&#x2009;0.01), though the clinical relevance is uncertain. VBSO was associated with reduced risks of graft subsidence (RR 0.23; p&#x2009;<&#x2009;0.01), pseudarthrosis (RR 0.25; p&#x2009;<&#x2009;0.01), revision surgery (RR 0.17; p&#x2009;<&#x2009;0.01), and neurological deterioration (RR 0.17; p&#x2009;=&#x2009;0.02). CSF leakage appeared to be less frequent with VBSO, but the difference was not statistically significant. VBSO was also associated with greater postoperative cervical lordosis and shorter hospital stays. However, these findings must be interpreted with extreme caution: leave-one-out sensitivity analyses revealed that the results for postoperative JOA score, neurological deterioration, and pseudarthrosis were fragile and driven by a single large study, meaning these apparent advantages may not be robust. In addition, GRADE assessment revealed very low certainty across all assessed outcomes. Given the very low certainty of evidence, the preliminary nature of the available data, the fragility of several key findings, and the critical limitations of the underlying studies (single institution, overlapping patient cohorts, developer bias, and systematic imbalance in follow-up duration), the observed differences should be considered hypothesis-generating rather than definitive. VBSO should not be considered a proven superior alternative to ACCF based on the current evidence. Prospective, multicenter, international studies with balanced follow-up durations conducted by independent surgical teams are required before broader adoption can be recommended.

Humans

Acute mitochondrial toxicity of caffeine in cultured heart cells.

The cytotoxic effect of caffeine on heart cells was evaluated in primary cultures of rat heart muscle (M) and endothelioid (E) cells. The cultures were exposed to 5, 10, or 20 mM caffeine for 6, 12, or 24 hours. As an index of cytotoxicity produced by the treatments, in situ changes in mitochondrial membrane fragility were measured by a sensitive cytochemical technique. The 24 hr treatment with 20 mM caffeine was lethal to both E and M cell cultures; only the 12 hr treatment of M cell cultures with 20 mM caffeine produced significant labilization of mitochondrial membranes. The results of tests with other concentrations and durations of treatment were not statistically significant.

Animals

The effect of megadose ascorbate on some haemopoietic factors in the young guinea pig.

The effect of oral administration of megadoses of ascorbate was studied on some haemopoietic factors in young apparently normal guinea pigs. Supplementation of 150 mg of the vitamin for 7 days resulted in significantly increased haematocrit value and haemoglobin concentration. Total and unsaturated iron binding capacity were also increased in association with elevated plasma iron concentration. The difference of these results from the control animals, however, was not statistically significant. The improved haematological status in guinea pigs by ascorbate treatment could be attributed to haemoconcentration rather than to an effect of iron metabolism.

Animals

Assessment of calcium dobesilate in diabetic retinopathy. A double-blind clinical investigation.

In this double-blind, randomized trial, which lasted for 2 years, the authors investigated the efficacy of calcium dobesilate on diabetic retinopathy. 68 patients (51 on the active substance, 17 on placebo) participated in the study. The statistical analysis of the results indicate that calcium dobesilate acts as a potent angioprotector, capable of preventing both intra and extraretinal hemorrhages. The drug also lowers the incidence of exudate formation and improves visual acuity.

Benzenesulfonates

Iron nutrition in infancy: effect of an iron-fortified milk formula.

Iron nutrition in infants was studied in a double-blind trial with artificial milk formula. Statistically significant differences were observed with the iron-fortified formula. Not all haematological indices showed significant differences. The fragiligraph technique result was the only parameter showing differences not influenced by other variables examined.

Animals

The lysosomal permeability test modified for toxicity testing with cultured heart endothelioid cells.

A modified lysosomal fragility test is described which is suitable for use with cultured cells. The permeability (fragility) of the lysosomal membranes of the cells to the substrate beta-glycerophosphate is measured by assessing the degree of particulate lysosomal straining seen after exposing the cells to the Gomori acid phosphatase staining reaction under carefully controlled conditions. Monolayer cultures of endothelioid cells from the hearts of neonatal rats have been used in all experiments. The time-course of lysosomal straining for cells exposed to various treatments (normal saline, isotonic sucrose, 0.25 m sucrose, distilled water, acetate buffer pH 5.0, cold acetone, neutral formalin, acetic-ethanol, Triton X-100, hydrocortisone, choloroquine and vitamin A) was compared with that of control cells stained under identical conditions. Statistical differences in staining between the test and control cells were determined by the Wilcoxin Signed Rank Test and also by regression analysis following a transformation designed to allow for the saturation character of the reaction. The success of the modified technique depends upon meticulous methodology. It is capable of demonstrating both lysosomal membrane labilization and stabilation, second- and third-stage lysosomal activation, and apparent lysosomal enzyme loss or destruction in situ. The technique also allows the degree of reversible or first-stage lysosomal activation to be subdivided on an almost continous basis and is suitable for investigating the effects of drugs and other agents on the integrity of the lysosome in situ.

Animals

Unveiling metabolic pathways in the hyperglycemic bone: bioenergetic and proteomic analysis of the bone tissue exposed to acute and chronic high glucose.

BACKGROUND: Bone fragility due to poor glycemic control is a recognized complication of diabetes, but the mechanisms underlying diabetic bone disease remain poorly understood. Despite the importance of bioenergetics in tissue functionality, the impact of hyperglycemia on bone bioenergetics has not been previously investigated. OBJECTIVE: To determine the effects of high glucose exposure on energy metabolism and structural integrity in bone tissue using an ex vivo organotypic culture model of embryonic chick femur. METHODS: Femora from eleven-day-old Gallus gallus embryos were cultured for eleven days under physiological glucose conditions (5.5&#xa0;mM, NG), chronic high glucose exposure (25&#xa0;mM, HG-C), or acute high glucose exposure (25&#xa0;mM, HG-A). Bioenergetic assessments (Seahorse assays), proteomic analysis (liquid chromatography-mass spectrometry), histomorphometric and microtomographic evaluations, and oxidative stress measurements (carbonyl content assay) were performed. Statistical analyses were conducted using IBM&#xae; SPSS&#xae; Statistics (v26.0). The Mann-Whitney nonparametric test was used for group comparisons in microtomographic analysis, ALP activity, and carbonyl content assays. For Seahorse assay results, ANOVA with Tukey's post-hoc test was applied after confirming data homoscedasticity with Levene's test. RESULTS: Chronic high glucose exposure reduced bone mineral deposition, altered histomorphometric indices, and suppressed key osteochondral development regulators. Acute high glucose exposure enhanced glycolysis and oxidative phosphorylation, while chronic exposure caused oxygen consumption uncoupling, increased ROS generation, and downregulated mitochondrial proteins critical for bioenergetics. Elevated oxidative stress was confirmed in the chronic high glucose group. CONCLUSION: Chronic high glucose exposure disrupted bone bioenergetics, induced mitochondrial dysfunction, and compromised bone structural integrity, emphasizing the metabolic impact of hyperglycemia in diabetic bone disease.

Animals

Long-term mortality in pediatric sepsis: a systematic review and meta-analysis.

BACKGROUND: Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols. METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software. RESULTS: A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I2 = 98.2%, p&#x2009;<&#x2009;0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited. CONCLUSION: Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.

Humans

Adaptive differentiation of murine lymphocytes. II. The thymic microenvironment does not restrict the cooperative partner cell preference of helper T cells differentiating in F1 leads to F1 thymic chimeras.

The cooperating preference of helper T cells originating from F1 bone marrow, but differentiating in adult thymectomized, lethally irradiated F1 recipients reconstituted with either f1 or homozygous parental thymus grafts was investigated. Cooperating preference was assayed by determining the levels of helper activity provided by antigen-primed T cells derived from such thymic chimeras for hapten-primed B lymphocytes obtained from conventional F1 or parental donors in adoptive secondary antibody responses in vivo. The results of these analyses revealed a tendency of helper T cells derived from parental thymic chimeras to provide better help for B cells of the same parental type corresponding to the origin of the thymus graft than for the opposite parent. Such preference was, however, only marginal and rarely were differences in levels of helper activity provided to the respective parental types statistically significant. Moreover, this marginal preference, when observed, pertained only to responses of the IgG class; no concordant preference in providing helper activity for IgE antibody responses was observed even with the same populations of thymic chimera helper T cells. Finally, in no instance was there any evidence of restriction in the classical sense of presence versus absence of help as we have routinely observed in all of our previous studies concerning genetic restrictions of T-B-cell cooperative interactions. Although the basis for differences in the studies reported here when compared to observations made in cytotoxic T-lymphocyte systems is unclear, and could reflect genuine mechanistic requirements concerning what directs H-2 restrictions in helper T cells and cytotoxic T lymphocytes, respectively, it is also possible that we are placing too much faith in our interpretations of data obtained in bone marrow chimera systems than is perhaps justified by the potentially great fragility of such systems.

Animals