Outcomes of HLA-mismatched HSCT with TCRαß/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity.

HLA-mismatched transplants with either in vitro depletion of CD3+TCRαß/CD19 (TCRαß) cells or in vivo T-cell depletion using post-transplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEI). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEI undergoing first transplant between 2010-2019 from an HLA-mismatched donor using TCRαß (n=167) or PTCY (n=139). Median age at HSCT was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84%) after TCRαß and 66% (57-74%) after PTCY (p=0.013). Pre-HSCT morbidity score (hazard ratio (HR) 2.27, 1.07-4.80, p=0.032) and non-Busulfan/Treosulfan conditioning (HR 3.12, 1.98-4.92, p<0.001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50-66%) after TCRαß and 57% (48-66%) after PTCY (p=0.804). Cumulative incidence of severe acute GvHD was higher after PTCY (15%, 9-21%) than TCRαß (6%, 2-9%, p=0.007), with no difference in chronic GvHD (PTCY, 11%, 6-17%; TCRαß, 7%, 3-11%, p=0.173). The 3-year GvHD-free EFS was 53% (44-61%) after TCRαß and 41% (32-50%) after PTCY (p=0.080). PTCY had significantly higher rates of veno-occlusive disease (14.4% versus TCRαß 4.9%, p=0.009), acute kidney injury (12.7% versus 4.6%, p=0.032) and pulmonary complications (38.2% versus 24.1%, p=0.017). Adenoviraemia (18.3% versus PTCY 8.0%, p=0.015), primary graft failure (10%, versus 5%, p=0.048), and second HSCT (17.4% versus 7.9%, p=0.023) were significantly higher in TCRαß. In conclusion, this study demonstrates that both approaches are suitable options in IEI patients, although characterized by different advantages and outcomes.

Critical-size defects reconstruction with four different bone grafts associated with e-PTFE membrane: A histomorphometric experimental in vivo study.

OBJECTIVES: The goal of this study was to assess the newly formed bone and the remnant biomaterial by comparing four different bone grafts used to treat critical-size defects, associated or not with the non-resorbable membrane. MATERIALS AND METHODS: Two calvaria critical-size bone defects were created in 50 male Wistar rats. They were divided into blood (G1), autogenous (G2), bioglass (G3), hydroxyapatite (G4), and xenograft (G5) groups, associated or not with e-PTFE. The experimental periods were 15 and 45 days. Sections were prepared for histomorphometric assessment. All data were analyzed by the mixed-effects model with multiple comparisons (significance level, p < .05). RESULTS: A similar level of new bone was observed for all groups, associated with a high level of vascularization. G1 and G2 ensured sovereignty over the greater quantity of new bone. A non-significant result was reported comparing groups with and without membranes. No significant result was found between the experimental synthetic biomaterials (G3 and G4). G5L achieved 22.0% of new bone after 45 days (p > .05). All groups had a stable volume of biomaterial kept in the short term (p > .05). G2 was the best material for new bone formation and final volume of biomaterial, followed by G4 < G5 < G3. Thus, it is possible that G4 had a better degradation profile among the experimental groups. CONCLUSIONS: The best results were found in the autogenous group, with higher resorption and integration; non-significative new bone was found among the experimental groups; and the regeneration of critical bone defects using an e-PTFE barrier did not present significant results on new bone formation.

An overview of vinasse pollution in aquatic ecosystems in Brazil.

We review the negative impacts of vinasse, a byproduct of alcohol distillation, on Brazil's freshwater ecosystems. We found a total of 37 pollution events between the years 1935 and 2023, with this number almost certainly an underestimate due to underreporting and/or unassessed events. Pollution by vinasse occurred both through accidents (e.g., tank failure) and deliberately (i.e., opening of floodgates), although in many cases the causes remain undetermined. All pollution events caused fish kills, with some records reporting negative effects on other organisms as well (i.e., crustaceans and reptiles). Pollution by vinasse, and associated negative effects, was reported for 11 states, with a notable number of cases in São Paulo. Most cases of vinasse pollution and negative impacts on biodiversity were recorded in rivers, followed by streams and reservoirs. Some of the affected river systems harbour threatened freshwater fishes. Hydrological connectivity means that pollution could have propagated along watercourses. Given these consequences of vinasse pollution on biodiversity, ecosystem functioning and services, we recommend a number of remedial actions.

Minimally invasive periodontal regeneration with the buccal approach: a systematic review and meta-analysis of clinical studies.

OBJECTIVE: The aim of this study was to investigate clinical periodontal parameters after treatment using the Minimally Invasive Surgical Technique (MIST), Modified Minimally Invasive Surgical Technique (M-MIST), and/or any technique for papilla preservation, such as Entire Papilla Preservation (EPP), modified-papilla preservation technique (M-PPT), or simplified-papilla preservation technique (SPPT). METHODS: The focus question was "For patients with periodontal intrabony defects (P), what is the best minimally invasive regenerative approach (I), comparing MIST, M-MIST, and papilla preservation techniques' outcomes (C) to improve PD, CAL, GR, and periodontal stability (O)?" An online search was conducted on PubMed, Cochrane Library, and Embase. Only randomized clinical trials and case series with a minimum of 10 enrolled patients were included. The risk of bias was evaluated using the Critical Appraisal tools in JBI Systematic Reviews. The meta-analysis compared the data obtained for the periodontal parameters analyzed, and the heterogeneity was verified. RESULTS: After the screening, nine articles were included. Seven studies applied MIST and its modifications; two used M-PPT, one SPPT, and one approached EPP. A general statistically significant PD reduction and CAL gain were noted between the groups, comparing baseline and follow-up for all articles, independently of the technique or materials used. Also, all studies showed a non-significant increase in the gingival recession. Four studies had a low risk of bias, four had a moderate risk, and only 1 had a high risk. Moderate heterogeneity was found in one analysis for CAL (65.73%); moderate and substantial heterogeneity was found in the PD results (71.91% and 89.19%); and no heterogeneity was found within all analyses for gingival recession (0%). CONCLUSION: MIST, M-MIST, and papilla preservation techniques demonstrated their potential and efficacy to improve periodontal conditions of sites with intrabony defects with minimal morbidity.

Efficacy of bioactive materials in preventing Streptococcus mutans-induced caries on enamel and dentine.

The study investigated the ability of bioactive materials used to restore enamel and dentine specimens to prevent caries. Enamel (n = 50) and dentine (n = 50) specimens were obtained from bovine incisors, prepared, and randomly allocated to one of five groups according to the restorative treatment: alkasite without adhesive system; alkasite with adhesive system; high viscosity glass ionomer cement; resin composite; no restoration; negative control group. Specimens were restored, exposed to a thermal cycling aging protocol, sterilized, and exposed to a cariogenic challenge induced by Streptococcus mutans and then submitted to surface and subsurface microhardness tests and polarized light microscopy to verify the caries lesion development in enamel or dentine surrounding the restorative materials. Data were analyzed using one-way ANOVA. In enamel and dentine, glass ionomer cement, alkasite without and with adhesive system presented a lower percentage surface microhardness loss than resin composite and negative control. Enamel subsurface microhardness presented no statistically significant differences between glass ionomer cement, alkasite without and with adhesive system. Glass ionomer cement also did not present statistically significant differences from resin composite and the negative control. In dentine, glass ionomer cement showed the highest subsurface microhardness values. In conclusion, bioactive restorative materials provide greater protection to enamel and dentine against surface caries development than resin composite.

Breast cancer survival after mammography dissemination in Brazil: a population-based analysis of 2,715 cases.

BACKGROUND: This study aims to assess breast cancer survival rates after one decade of mammography in a large urban area of Brazil. METHODS: It is a population-based retrospective cohort of women with breast cancer in Campinas, São Paulo, from 2010 to 2014. Age, vital status and stage were accessed through the cancer and mortality registry, and patients records. Statistics used Kaplan-Meier, log-rank and Cox's regression. RESULTS: Out of the 2,715 cases, 665 deaths (24.5%) were confirmed until early 2020. The mean age at diagnosis was 58.6 years. Women 50-69 years were 48.0%, and stage I the most frequent (25.0%). The overall mean survival was 8.4 years (8.2-8.5). The 5-year survival (5yOS) for overall, 40-49, 50-59, 60-69, 70-79 years was respectively 80.5%, 87.7%, 83.7%, 83.8% and 75.5%. The 5yOS for stages 0, I, II, III and IV was 95.2%, 92.6%, 89.4%, 71.1% and 47.1%. There was no significant difference in survival in stage I or II (p = 0.058). Compared to women 50-59 years, death's risk was 2.3 times higher for women 70-79 years and 26% lower for women 40-49 years. Concerning stage I, the risk of death was 1.5, 4.1 and 8.6 times higher, and 34% lower, respectively, for stage II, III, IV and 0. CONCLUSIONS: In Brazil, breast cancers are currently diagnosed in the early stages, although advanced cases persist. Survival rates may reflect improvements in screening, early detection and treatment. The results can reflect the current status of other regions or countries with similar health care conditions.

Do bioactive materials show greater retention rates in restoring permanent teeth than non-bioactive materials? A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVES: To answer the following research question: does the clinical evaluation of restorations on permanent teeth with bioactive materials show greater retention rates than those with non-bioactive materials? MATERIALS AND METHODS: A search strategy was used in the following databases: MEDLINE via PubMed, Scopus, Web of Science, LILACS, BBO, Embase, The Cochrane Library, and OpenGrey. Randomized controlled trials (RCTs), with a minimum of 2-year follow-up and evaluating at least one bioactive material in permanent teeth were included. Risk of bias was detected according to the Cochrane Collaboration tool for assessing the risk of bias (RoB 2.0), and network meta-analysis was performed using a random-effects Bayesian-mixed treatment comparison model. RESULTS: Twenty-seven studies were included. The success of the restorations was assessed using modified USPHS system in 24 studies and the FDI criteria in 3 studies. Network meta-analysis revealed three networks based on restoration preparations. Resin composites were ranked with higher SUCRA values, indicating a greater likelihood of being the preferred treatment for class I, II, and III restorations. In class V, resin-modified glass ionomer cement was ranked with the highest value. CONCLUSION: Bioactive restorative materials showed similar good clinical performance in terms of retention similarly to conventional resin composites. CLINICAL SIGNIFICANCE: The findings must be interpreted with caution because many RCT on restorative materials aim to verify the equivalence of new materials over the gold standard material rather than their superiority. The present systematic review also suggests that new RCT with longer follow-up periods are necessary.

The Interference of Age and Gender on Smile Characterization Analyzed on Six Parameters: A Clinical-Photographic Pilot Study.

Background and Objective: This study aimed to evaluate six smile-esthetic parameters (deviation of the upper dental midline from the facial midline, upper lip curvature, smile line, smile arch, smile width, and shape of the maxillary central incisors), correlating them with age and gender. Materials and methods: Caucasian individuals (N = 114) were grouped by gender (male and female) and age (group I-18 to 30 years old; group II-31 to 50 years old; and group III-over 50 years old). Using a digital camera, extra and intraoral pictures were taken to analyze the variables above-mentioned. The data were statistically evaluated, considering a significance level of p < 0.05. Results: Most participants found deviations of the upper dental midline, straight upper lip curvature, and the medium smile line coincided with the facial midline. The parallel smile arch exposing 9 to 11 upper teeth, the absence of exposure of lower teeth when smiling, and oval upper incisors were prevalent parameters. Regarding gender, significant results were found for the curvature of the upper lip (p = 0.049), the smile arch (p = 0.001), and the shape of the upper central incisors (p = 0.004). For age, the association with the curvature of the upper lip (p = 0.032), the smile line (p = 0.001), the smile arch (p = 0.007), the width of the smile exposing lower teeth (p = 0.002), and the shape of the upper central incisors (0.012) were significant. Conclusions: Within this study's limitations, gender and age affect the anterior teeth shape and upper lip curves; gender and age did not influence the coincidence between dental and facial midlines.

Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults.

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged <18 years) and 77 adults. Median follow-up was 45 months. Median age at transplantation was 7 years (range, 0.1-48.6). Kaplan-Meier estimates of overall survival (OS) and event-free survival (EFS) at 3 years were 85.7% and 75.8%, respectively. In multivariate analysis, older age was associated with reduced survival and increased chronic graft-versus-host disease. Nevertheless, OS and EFS at 3 years for patients ≥18 years were 76% and 69%, respectively. Use of 1-antigen-mismatched donors was associated with reduced OS and EFS . No significant difference was found in OS, but a significantly reduced EFS was noted in the small group of patients who received a transplant from a donor with a >1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.

Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype.

Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID). These drugs are associated with severe side effects such as gastric ulcers, gastritis, or internal bleeding. One of NSAIDs, Dipyrone® (metamizole) is largely used in many European and South American countries despite its dubious effectivity and its withdrawal from the market of several countries. Here, aiming to identify a new anti-inflammatory drug prototype based on Dipyrone® structure, a set of 27 molecules were virtually screened, and 4 compounds containing the active metabolite 4-aminoantipyrine and 1,4-dioxo-2-butenyl fragment were selected for docking, synthesis, and biological evaluation. The selection was based on the number of H-bonds and π- π stacking interactions between the inhibitor and the amino acids within the binding site of the enzyme. Carrageenan-induced paw edema, acetic acid-induced writhing, and formalin assays were used to evaluate inflammation and pain response. The selected compounds 1-4 inhibited the involvement of biogenic amines in the formation of paw edema. Compounds 1-4 also reduced pain in the inflammatory response phase. It has to be noted that 4-AA may cause agranulocytosis, which should be borne in mind when developing drug candidates of similar structure. Our new drug prototypes based on 4-aminoantipyrine and 1,4-dioxo-2-butenyl moieties open a gate for developing a prototype of nonsteroidal anti-inflammatory drugs.

Inspiratory muscle training in addition to whole body vibration for functional and physical outcomes in pre-frail older women: a randomized controlled trial.

BACKGROUND: to investigate the efficacy of addition of inspiratory muscle training (IMT) to the whole body vibration (WBV) on functional outcomes, physical performance, muscle strength and metabolism in pre-frail older women. METHODS: this study was a randomized double-blind trial. Forty-two older women aged 60-80 years who meet the Cardiovascular Health Study frailty criteria for pre-frailty were randomly allocated to IMT + WBV, IMTsham + WBV or Sham groups. IMT + WBV group received 12 weeks of both trainings, whereas IMTsham + WVB received 12 weeks of WBV alone. Sham group received 12 weeks of IMT with a low fixed load and were positioned at the vibratory platform without therapeutic effect. Participants were evaluated before and after the intervention for the following outcomes: 6-min walk test distance (6MWD), balance using Tinetti test, functional mobility using timed up and go test (TUG), handgrip strength (HGS) and peripheral muscle metabolism (glucose and lactate levels). RESULTS: after the training, both groups IMT + WBV and IMTsham + WBV improved 6MWD [mean percentage changes = 20.31 (SD = 14.62) and 13.02 (SD = 12.14), respectively] compared with Sham [0.27 (SD = 6.51)], P <0.01. There was also a significant decrease of mean percentage changes on time of the TUG for IMT + WBV [-21.87 (SD = 7.87)] and IMTsham + WBV [-11.15 (SD = 13.64)] compared with Sham [-4.25 (SD = 13.25)], P <0.01. IMT + WBV group improved balance when compared with IMTsham + WBV and Sham groups (P <0.05 and < 0.01, respectively). HGS and levels of lactate and glucose were similar between groups. CONCLUSIONS: the addition of IMT to the WBV was effective to improve functionality, balance and physical performance in pre-frail older women.

Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adults.

BACKGROUND: COPD is associated with an abnormal lung immune response that leads to tissue damage and remodeling of the lung, but also to systemic effects that compromise immune responses. Cigarette smoking also impacts on innate and adaptative immune responses, exerting dual, pro- and anti-inflammatory effects. Previously, we showed that COPD patients presented accelerated telomere shortening and decreased telomerase activity, while, paradoxically, cigarette-smokers exhibited preserved telomerase activity and slower rate of telomere shortening. RESULTS: Here, we evaluated the naive, CM, EM and TEMRA subsets of TCD4 and TCD8 cells according to the expression of CCR7/CD45RA. We compared age-matched COPD patients, cigarette-smokers without clinical-laboratory evidence of pulmonary compromise, and healthy individuals. They were additionally compared with a group of young adults. For each subset we analysed the expression of markers associated with late differentiation, senescence and exhaustion (CD27/CD28/CD57/KLRG1/PD1). We show that COPD patients presented a drastically reduced naive cells pool, and, paradoxically, increased fractions of naive cells expressing late differentiation, senescence or exhaustion markers, likely impacting on their immunocompetence. Pronounced phenotypic alterations were also evidenced in their three memory T-cell subsets compared with the other aged and young groups, suggesting an also dysfunctional memory pool. Surprisingly, our smokers showed a profile closer to the Healthy aged than COPD patients. They exhibited the usual age-associated shift of naive to EM TCD4 and TCD8 cells, but not to CM or TEMRA T-cells. Nonetheless, their naive T-cells phenotypes were in general similar to those of the Youngs and Healthy aged, suggesting a rather phenotypically preserved subset, while the memory T-cells exhibited increased proportions of cells with the late-differentiation or senescence/exhaustion markers as in the Healthy aged. CONCLUSION: Our study extends previous findings by showing that COPD patients have cells expressing a full range of late differentiated, senescent or exhausted phenotypes encompassing all TCD4 and TCD8 subsets, consistent with a premature immunosenescence phenotype. Surprisingly, the smokers group's results suggest that moderate to heavy chronic cigarette smoking did not accelerate the pace of immunosenescence as compared with the Healthy aged.

Hospitalization is associated with handgrip strength decline in older adults: a longitudinal study.

BACKGROUND: Hospitalization episodes in older people are considered critical events because they act in a complex interaction among immobilization effects. AIM: The purpose of this study was to evaluate the effects of hospitalization on older adults' handgrip strength (HGS) and to identify factors related to its performance on the test. METHODS: A cohort study was conducted in a hospital in Natal, Brazil, and enrolled all patients aged 60 years and older between January 2014, and April 2015. Cognitive (Leganés Cognitive Test) and functional status (Katz Index, Lawton Scale and Functional limitation Nagi), physical performance (HGS and gait speed) and depressive symptom assessment (GDS-15) were evaluated at admission and discharge time, as well as information about health and functional status prior to hospitalization. Linear Mixed Models were used to create a predictive model for handgrip strength. RESULTS: A total of 1168 hospitalized older adults were evaluated. A significant decrease in HGS means was observed between admission and discharge time for men (28.12 ± 10.35 and 20.22 ± 14.08 Kgf, p < 0.01) and for women (19.18 ± 7.87 and 14.88 ± 9.79 Kgf, p < 0.01). Undergoing surgery and basal values of the Katz Index were associated with worse HGS performance at discharge. CONCLUSION: A significant decline in handgrip strength during the hospitalization period was observed, which was more pronounced in men. Performing surgery during hospitalization was an important factor for HGS decline in men and women. This study reinforces the importance of early mobilization and muscle strength loss prevention protocols in hospitalized older patients.

Vaginal stretching therapy and class IIIB vaginal laser treatment for pelvic floor myofascial pain: a randomized clinical trial.

PURPOSE: Several treatment options are proposed for the management of pelvic floor myofascial pain (PFMP). Manual therapy, such as vaginal stretching (VS), is one of these options. Photobiomodulation therapy (PBMT) with a laser device is a treatment option for PFMP that has been tested on other muscles. The aim of this study was to evaluate the effect of VS combined or not with PBMT for PFMP treatment. METHODS: One hundred three women with PFMP were enrolled in a double-blind randomized trial and assigned to VS+PBMT (10 treatments over 2 weeks with 100 mw delivering 12 joules to surface intravaginally, using near-infrared light 808 nm) and VS+shamPBMT treatment groups. Pain severity was assessed by Visual Analog Scale (VAS). Pelvic floor muscle function was assessed by Oxford Scale and surface electromyography. Urinary symptoms were evaluated by ICIQ-OAB and ICIQ-SF questionnaires, and intestinal constipation was assessed by ROMA criteria. RESULTS: There was a significant improvement in pain intensity (VAS) after treatment in both groups, with no difference between groups (p = 0.46). More than 50% of the women complained of severe pain before treatment, and after treatments, it was reported by less than 20% of women (p < 0.001), with no difference between groups (p = 0.08). Urinary symptoms improved in both groups (p < 0.001) with no difference between groups (p = 0.37). Intestinal constipation improved in the VS+PBMT group only (p = 0.01). CONCLUSION: VS and VS with near-infrared vaginal laser therapy were equally effective at decreasing myofascial pelvic pain and reducing urinary symptoms TRIAL REGISTRATION: REBEC (Registro Brasileiro de Ensaios Clínicos; Brazilian Registry of Clinical Trials) under no.RBR-2TDCQ4 (November 11, 2018).

Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Assessment of nitric oxide metabolites concentrations in plasma, saliva, and breast milk and their relationship in lactating women.

Nitric oxide (NO) plays a role in many biological mechanisms. The amounts of physiologically produced NO are associated with the concentrations of its metabolites nitrate and nitrite. This study investigated whether there is any association between the concentrations of NO metabolites nitrate, nitrite, and nitrosylated species (RXNO) in mature breast milk, saliva, and plasma in healthy lactating women (N = 30). We hypothesized that the NO metabolites concentrations in plasma are associated with those found in saliva and in breast milk. NO metabolites concentrations were measured using chemiluminensce-based assays. Nitrate concentrations in breast milk are twice as much as plasma concentrations, whereas nitrate concentrations in saliva are about eightfold higher (both P < 0.001). Similar differences were found when nitrite concentrations were taken into consideration. RXNO concentrations in breast milk were negligible, and RXNO concentrations in saliva were approximately sixfold higher than those found in plasma samples (P < 0.0001). Nitrate concentrations in plasma are associated with nitrate concentrations in saliva (rs = 0.474, P = 0.004). However, no significant association was found between nitrate concentrations in breast milk and in plasma (P > 0.05). Our results show a significant association between nitrate concentrations in plasma with those found in saliva, whereas all other relationships were not significant. In conclusion, this report shows for the first time that the physiological concentrations of NO metabolites in human breast milk are probably independent of circulating NO metabolites concentrations and may depend mostly on endogenous NO synthesis in the breast. These findings may have clinical implications for newborns and lactating women.

Influence of different warming temperatures on the vitrified testicular fragments from pre-pubertal cat.

Testicular vitrification is an alternative to preserve the genetic material of pre-pubertal animals. However, there are few studies on post-vitrification warming. Hence, the aim was to compare the influence of different warming temperatures on vitrified testicular fragments from pre-pubertal cats. The testicles were fragmented and divided into a control group (non-vitrified) and vitrified, using an association between dimethylsulphoxide and glycerol. The vitrified fragments were warmed at 50, 55 and 60°C/5 s. Morphological and morphometric evaluations were carried out using classical histology. Afterwards, the mitochondrial activity was evaluated using Rhodamine 123. The data were expressed in mean and standard error. The differences were considered significant when p < .05. In the histomorphological analysis, the testicular fragment presented seminiferous tubules with poorly developed germinal epithelium, compatible with pre-pubertal animals. The group warmed at 50°C presented similar to the control regarding the maintenance of the integrity of the tubules and cells, without stromal rupture and lamina propria alteration, as well as regarding the maintenance of the junctions between the cells. The group warmed at 55°C showed reduction of the cell junctions, and the one warmed at 60°C had increased detachment of the basement membrane (p < .05). The warming caused a reduction in the tubular diameter inversely proportional and progressive to the increase in temperature, with the highest diameter in the control group and the lowest in the 60°C group. The control group showed a lower incidence of Rhodamine 123, followed in ascending order of the warmings at 55 and 60°C. The higher mitochondrial activity was obtained with 50°C, showing an increase of the metabolic cell function at this temperature. It was concluded that the testicular fragment of pre-pubertal cats presents a better preserved morphology, morphometry and viability when warmed at 50°C.

Radiotherapy for locally advanced head and neck cancer in elderly patients: results and prognostic factors a single cohort.

BACKGROUND: The objective of this study was to assess the treatment outcomes and prognostic factors of elderly patients with locally advanced head and neck cancer (LAHNC) undergoing radiotherapy (RT). MATERIALS AND METHODS: A retrospective cohort from a single institution, from 2000 to 2015, including patients older than 65 years old with LAHNC (stage III-IVa) treated by RT combined or not with chemotherapy (CRT). Univariate and multivariate analysis (MVA) were performed to identify prognostic factors associated with overall survival (OS), cancer-specific survival (CS), and locoregional control (LRC). A p-value < 0.05 was considered significant. RESULTS: 220 patients with LAHNC and > 65 years of age were identified. The median follow-up was 3.8 years, the 3/5 years estimated OS, CS, and LRC rate was 40%/30%, 49%/34%, 76%/45%, respectively. In the univariate analysis, clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.035), Karnofsky performance status (KPS, 60-70, p = 0.03) and tumor site (other than vs. hypopharynx, p = 0.0001) were associated with lower OS. Patients with clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.015), N stage (N0/1 vs. N2/3, p = 0.04), (KPS 60-70, p = 0.04) and tumor site (other than vs. hypopharynx, p = 0.0001) had worst CS. For the LRC, clinical stage (III vs. IVa/b, p = 0.02), tumor stage (T1/2 vs. T3/4, p = 0.02), treatment type (CRT vs. RT, p = 0.02), RT technique (IMRT vs. 2DRT/3DRT, p = 0.0001), and tumor site (other than vs. hypopharynx, p = 0.02) were significant. In the MVA, KPS maintained significant for OS and CS. For LRC, clinical stage (Iva/b, p = 0.007), tumor stage (T3/4, p = 0.047) and radiotherapy technique other than IMRT (p = 0.0001) were significant. CONCLUSION: The OS, CS, and LRC were associated with several prognostic factors. The clinical performance was the main marker of OS and CS. Chemoradiation should be offered to selected elderly patients using IMRT to improve LRC.

Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases.

Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/µL CD4+ and 1000/µL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (>3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P < .0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.