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Purpose: To evaluate the safety of the Fecal Microbial Transplant for Sjogren Syndrome (FMT) trial in individuals with immune-mediated dry eye (DE). Design: Open-label, nonrandomized clinical trial. Methods: The study population included 10 individuals with DE symptoms and signs meeting criteria for Sjogren or positive early Sjogren markers. Procedures were 2 FMTs from a single healthy donor delivered via enema, 1 week apart. The primary outcome measure was safety. In addition, gut microbiome profiles, DE metrics, and T-cell profiles in blood were examined at baseline before FMT, and at 1 week, 1 month, and 3 months after FMT. Results: The mean age of the population was 60.4 years; 30% were male; 50% were white; and 50% were Hispanic. At baseline, all subjects had significantly different gut microbiome profiles from the donor, including higher mean diversity indices. Subjects had a decreased abundance of genera Faecalibacterium, Prevotella, and Ruminococcus and an increased abundance of genera Alistipes, Streptococcus, and Blautia compared to the donor. Effector and regulatory T-cell profiles were positively correlated with each other and with DE symptom severity (T helper 1 cells [Th1]; r = .76; P = .01; Th17: r = 0.83; P = .003; CD25: r = 0.66; P = .04; FoxP3: r = 0.68; P = .03). No adverse events were noted with FMT. After FMT, gut microbiome profiles in 8 subjects moved closer to the donor's profile. As a group, gut microbiome profiles at all follow-up time points were more similar to the original recipients’ than the donor's microbiome; however, certain phyla, classes, and genera operational taxonomic unit (OTU) numbers remained closer to the donor vs recipients’ baseline profiles out to 3 months. Five individuals subjectively reported improved dry eye symptoms 3 months after FMT. Conclusions: FMT was safely performed in individuals with immune-mediated DE, with certain bacterial profiles resembling the donor out to 3 months after FMT. One-half the subjects reported improved DE symptoms. The most effective FMT administration method has yet to be determined.

Transient expression systems for plants have several advantages for the development of innovative plant-made vaccines. This technology has the potential to render veterinary vaccines against relevant diseases, such as paratuberculosis, a chronic intestinal infectious disease affecting livestock. This study showed that Agrobacterium-mediated transient transformation of maize seedlings allows the production of the Ag85B antigen from Mycobacterium avium subsp. paratuberculosis (MAP) at levels up to 11.35 µg g−1 dry weight. Moreover, BALB/c mice orally and subcutaneously immunized with the maize-made Ag85B vaccine produced specific IgG and IgA antibodies. Therefore, this platform is proposed as a rapid approach to produce the functional MAPAg85B antigen at sufficient yields to induce specific humoral immune responses in animal testing, which constitutes the first step in the development of a plant-made oral vaccine against paratuberculosis. This paper describes for the first time, the transient transformation of maize seedlings to produce Ag85B vaccine from Mycobacterium avium subsp. paratuberculosis. The plant-produced antigen showed strong immunoreactivity in immunized mice.

BackgroundSex is frequently underestimated as a prognostic biomarker in cancer. In this study, we evaluated a large cohort of patients and public datasets to determine the influence of sex on clinical outcomes, mutational status, and activation of immune pathways in different types of cancer.MethodsA cohort of 13,619 Oncosalud-affiliated patients bearing sex-unrelated cancers was followed over a 20-year period. Hazard ratios (HRs) for death were estimated for female vs. male patients for each cancer type and then pooled in a meta-analysis to obtain an overall HR. In addition, the mutational status of the main actionable genes in melanoma (MEL), colorectal cancer (CRC), and lung cancer was compared between sexes. Finally, a gene set enrichment analysis (GSEA) of publicly available data was conducted, to assess differences in immune processes between sexes in MEL, gastric adenocarcinoma (GC), head and neck cancer (HNC), colon cancer (CC), liver cancer (LC), pancreatic cancer (PC), thyroid cancer (TC), and clear renal cell carcinoma (CCRCC).ResultsOverall, women had a decreased risk of death (HR = 0.73, CI95: 8%–42%), with improved overall survival (OS) in HNC, leukemia, lung cancer, lymphoma, MEL, multiple myeloma (MM), and non-melanoma skin cancer. Regarding the analysis of actionable mutations, only differences in EGFR alterations were observed (27.7% for men vs. 34.4% for women, p = 0.035). The number of differentially activated immune processes was higher in women with HNC, LC, CC, GC, MEL, PC, and TC and included cellular processes, responses to different stimuli, immune system development, immune response activation, multiorganism processes, and localization of immune cells. Only in CCRCC was a higher activation of immune pathways observed in men.ConclusionsThe study shows an improved survival rate, increased activation of immune system pathways, and an enrichment of EGFR alterations in female patients of our cohort. Enhancement of the immune response in female cancer patients is a phenomenon that should be further explored to improve the efficacy of immunotherapy.

Peritoneal dialysis (PD) has many advantages compared to in-center hemodialysis, which include technical simplicity, and being a home therapy it allows patients significant autonomy for all their daily activities. Nephrologists require trustworthy information from patients for the appropriate management of PD, that is, a careful record of adherence to the prescribed schedule, effective time of dialysis, and a detailed volume of ultrafiltration (UF) is required. All these tasks demand time and commitment from patients, resulting frequently in incomplete or inconsistent information. Development and incorporation of remote monitoring devices to machines for automated PD makes data recovery easy and safe, and provides the medical team the opportunity to be more proactive, and prevent complications due to under dialysis, catheter dysfunction or chronic and acute changes in UF. Remote monitoring devices/machines may be a useful tool in the early diagnosis of peritoneal damage and even in the initial manifestation of peritonitis.

Osteoid osteoma represents approximately 10% to 11% of all the benign bone tumors. The localization at the articular and juxta-articular level of the knee is an atypical picture that causes both diagnostic and therapeutic problems. We present the case of an osteoid osteoma of the lateral tibial plateau just beneath the joint level. The lesion was removed by a rear-entry computed tomography (CT)-guided drill under arthroscopic control and the bony defect filled with bone graft harvested from the proximal tibial metaphysis. Postoperative CT scans at 3 months, and 1 and 2 years were performed. The result of the kneeling test to evaluate donor-site morbidity 1 year after the surgery was negative. There were no immediate or delayed complications. Currently (2 years postoperatively), the patient has no pain and has gone back to his normal active daily lifestyle and routines. The follow-up CT scan 2 years after surgery showed complete excision of the lesion and perfect positioning of the bone graft. This new approach/technique enabled us to avoid damaging the proximal structures, to examine the lesion, and to fill the bony defect. Moreover, as shown by CT scan at follow-up, iatrogenic lesions to the cartilage of the tibial plateau were not reported.

Our objective is to investigate which factors and patient characteristics are associated with success in Trabectome surgery. A total of 658 phakic cases with at least of 12 months follow-up were included in the analysis. Baseline demographics and medical data were collected. The main outcome measure was intraocular pressure (IOP), glaucoma medication (Rx), and secondary glaucoma surgery if any. Success was defined as IOP reduction of 20% or more from preoperative IOP and IOP < 21 mm Hg with no secondary surgery throughout the follow-up period. Risk factors for failure were determined by using univariate and multivariate cox regression. At baseline, the average IOP was 23.6 ± 7.8 mm Hg and the average number of medications was 2.6 ± 1.3 for all cases. At 12 months, the average IOP was 16.0 ± 3.6 mm Hg (P

The fabella is a sesamoid bone that can very occasionally act as a source of atypical knee pain, often mistaken for a more common cause of clinical symptoms, such as an intra-articular loose body or an osteophyte. We report a case of symptomatic dislocation of an osteoarthritic, enlarged fabella, 4 years after total excision of the patella for a comminuted fracture, that was primarily overlooked and led to repeated diagnostic arthroscopy of the knee. A thorough history and physical examination of the joint as well as appropriate roentgenographic studies could have spared this patient an unnecessary arthroscopy and indicated the correct therapy.

Objective: To assess the role of specific risk factors that may predispose preterm infants with mild or no initial respiratory distress syndrome to the development of chronic lung disease (CLD). Study design: Clinical data were collected prospectively from 119 ventilator- supported preterm infants with birth weights between 500 and 1000 gm, who survived more than 28 days and required fewer than 3 days of treatment with fraction of inspired oxygen >25% during the first 5 days of life. Logistic regression analysis was used in a multivariate assessment of risk factors for CLD. Results: Chronic lung disease occurred in 44 of the patients (37%). The analysis showed that low birth weight, patent ductus arteriosus (PDA), and sepsis were significant risk factors for CLD. The corresponding odds ratios for CLD and their 95% confidence intervals (CI) were as follows: 2.9 per 100 gm birth weight decrement (CI, 1.7 to 4.8); 6.2 (CI, 2.1 to 18.4) for PDA; and 4.4 (CI, 1.3 to 14.5) for sepsis. When sepsis and PDA occurred simultaneously, the odds ratio for CLD increased to 48.3 (CI, 6.3 to >100) in comparison with infants without these conditions. Episodes of PDA were categorized as either early (occurring during the first week of life) or late (after the first week), and the respective odds ratios for CLD were 2.8 (CI, 0.8 to 9.4) and 21.1 (CI, 5.6 to 80) in comparison with infants without PDA. For the duration of symptomatic PDA, the odds ratio for CLD was 3.5 per week that the PDA remained open (CI, 1.9 to 6.5). Conclusion: CLD is a frequent sequela in very low birth weight infants with mild or no respiratory distress syndrome. In this population, the development of late episodes of PDA, usually in association with a nosocomial infection, seems to play a primary role in the pathogenesis of CLD. (J P EDIATR 1995;126:605-10)

To investigate the role of genioglossus and posterior cricoarytenoid (PCA) activity in stabilizing the extrathoracic airway (ETA) of full-term infants during inspiratory flow-resistive loading (IRL), 10 unsedated full-term infants were evaluated in quiet sleep. IRLs were randomly imposed (L2, 125 cmH2O.l–1.s; L3, 250 cmH2O.l–1.s). Ventilation, total respiratory resistance (a correlate of ETA resistance), and moving time averages of PCA, submental activity of the genioglossus (SM), and diaphragm electromyogram were obtained. Results revealed no phasic activity in the SM during baseline breathing or with either IRL. Phasic PCA activity was always observed; burst duration increased with L2 and L3 (P < 0.01) and commenced earlier in relation to the onset of inspiratory airflow with both loads (P < 0.05). PCA activity always preceded that of the diaphragm and invariably outlasted it other than with L3. The upper airway negative pressure changes induced by IRL were insufficient to recruit SM activity; other potential stimuli such as transcutaneous PO2, transcutaneous PCO2, and pulmonary stretch receptor activation (increase in tidal volume) remained unchanged. Ventilation decreased with both loads (L3: P < 0.01), esophageal and mouth pressures increased (P < 0.01), and inspiratory time and inspiratory time divided by total time were both prolonged (P < 0.01). Total respiratory resistance remained unchanged with L2 but increased with L3 (P < 0.01). We concluded that ETA narrowing may be induced in full-term infants during quiet sleep with moderately large-sized IRL and that it is not entirely ameliorated by activation of the SM or PCA or by arousal.

Knee injuries in young athletes include not only the typical adult bone injuries, ligament and cartilage, but also the growth plate lesions. Osteochondroses are idiopathic, self-limited disturbance of enchondral ossification in which a rapid growth spurt is present. The patella could be affected by two different kinds of osteochondroses: Kohler syndrome and Sinding-Larsen-Johansson. Here we are reporting the first case of simultaneous location of osteochondroses of the two ossification centers of both patella. A 9-year-old boy, competitive skater, presented a history of anterior knee pain involving both knees. Standard X-rays, axial patellar view, MRI and arthro-MR were performed. In order to follow the natural history of the pathology and the evolution of the healing, examinations at 2 years were repeated. We proposed the young skater a medical and a physiotherapeutic treatment based on unloading, isometric exercises, NSAID. As the symptoms improve a gradual return to competitive sports activity was allowed. The case mentioned above can be considered an atypical case because the patient suffered for a bilateral knee osteochondroses, involving simultaneously the primary ossification centre (Kohler syndrome) and the secondary ossification centre (Larsen syndrome) of the patella.

Acetazolamide (ACTZ) reduces sleep apnea in adults exposed to high altitude and augments the ventilatory response to CO2. In order to determine the effect of ACTZ on the ventilatory response to CO2 and the incidence of apnea in preterm infants, 7 infants (BW, 1070 ± 191 g; postnatal age, 9 ± 7 days) were randomized to receive ACTZ (5 mg/kg/dose 06h for 36 hr) and 7 infants (BW, 1092 ± 292 g; post-natal age, 5 ± 2 days) received aminophylline (AMINO; 8 mg/kg bolus then 2.5 mg/kg Q12h for 36 hr). Minute ventilation (VE), end-tidal CO2, (P), ventilatory response to CO2 number of apneic episodes (≥15 sec duration), and arterial blood gases were measured before and 24–36 hr after starting therapy. In the AMINO group there was a significant decrease in apnea frequency from 6 ± 1 to 2 ± 2 episodes over an 8 hr epoch (P < 0.05), while no significant change was observed in the ACTZ group. The end-tidal CO2, decreased significantly from 44 ± 7 to 38 ± 6 mmHg in the AMINO group and from 47 ± 5 to 36 ± 5 mmHg in the ACTZ (P < 0.05), which lead to a shift to the left of the CO2,-response curve in both groups. The slope of the CO2, response curve did not change Significantly in the AMINO group and decreased in the ACTZ group. There was a significant decrease of pH from 7.43 to 7.26 in the ACTZ group, whereas in the AMINO group pH increased from 7.38 to 7.44. No significant changes in VE, tidal volume, respiratory rate, lung compliance, or resistance were observed with treatment in any of the two groups. These findings demonstrate that both AMINO and ACTZ decreased end-tidal CO2 and caused a shift of the CO2 response curve to the left. Despite these similar effects, ACTZ did not have an effect on apnea incidence. Pediatr Pulmonol. 1994; 17:291–295. © 1994 Wiley-Liss, Inc.