A comprehensive overview of eco-friendly bio-fertilizers extracted from living organisms.

Currently, sustainable agriculture involves ecofriendly techniques, which include biofertilization. Biofertilizers increase plant productivity by improving soil fertility and nutrient content. A wide range of living organisms can be applied as biofertilizers and increase soil fertility without causing pollution due to their biodegradability. The organisms can be microorganisms like bacteria, microalgae, and micro fungi or macro organisms like macroalgae, macro fungi, and higher plants. Biofertilizers extracted from living organisms or their residues will be increasingly used rather than chemical fertilizers, which cause heavy metal accumulation in soil. Biofertilizer use aims for sustainable development in agriculture by maintaining the soil. This will mitigate climate change and related impacts and will also lower many serious diseases resulting from pollution such as cancer, liver and renal failure, and immune diseases. This review is a comprehensive overview of biofertilizers extracted from a range of living organisms from the Kingdoms Monera to Plantae and included bacteria, algae, fungi, and higher plants. Organisms that play a vital role in elevating soil nutrients in a safe, cheap, and ecofriendly manner are included in the review to promote their potential commercial application.

Inflammatory Cytokines Are Associated with Cognitive Dysfunction and Depressive State during Acute Bacterial Infections and the Recovery Phase.

During a bacterial infection, individuals may present with behavioral changes referred to as sickness behavior, which has been suggested is induced by the inflammatory markers that are released because of the infective immunological challenge. However, few studies have explored this multidimensional phenomenon in naturally occurring conditions. A longitudinal observational study was conducted to explore the role of inflammatory cytokines in mediating the sickness behavior during a bacterial infection. There were 13, 11 and 37 participants in the infection, hospital control and healthy groups, respectively. They were all followed up for 6 weeks and their inflammatory markers were quantified throughout those weeks. Cognitive function and depressive state were assessed by means of the Mini-Mental State Examination (MMSE) and Cornell Scale for Depression in Dementia (CSDD). Reductions in proinflammatory markers C-Reactive protein (CRP), interleukin - 6 (IL6) and tumor necrosis factor-α (TNFα) and increments in anti-inflammatory markers (interleukin - 4 (IL4)) were associated with an improvement in CSDD and MSEE in patients recovering from a bacterial infection. The correlation between inflammatory makers and CSDD was statistically significant for the CRP (r = 0.535, p = 0.001), the IL6 (r = 0.499, p < 0.001), the TNFα (r = 0.235, p = 0.007) and the IL4 (r = -0.321, p = 0.018). Inflammatory cytokines may mediate sickness behavior during acute illness. These results may enhance the understanding of the pathophysiology and potential treatment strategies to palliate this sickness behavior.

Donor Cell Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation.

Approximately 25,000 allogeneic transplants are performed annually worldwide; a figure that has steadily increased over the past three decades. The study of transplant recipient survivorship has become a cogent topic and post-transplant donor cell pathology warrants further study. Donor cell leukemia (DCL) is a rare but serious complication of allogeneic stem cell transplantation (SCT) where the recipient develops a form leukemia originating from the donor cells used for transplantation. Detection of abnormalities predicting donor cell pathology might inform donor selection, and the design of survivorship programs for early detection of these abnormalities might allow therapeutic intervention earlier in the disease course. We present four recipients of allogeneic hematopoietic stem cell transplant (HSCT) from our institution who developed donor cell abnormalities allogeneic SCT, highlighting their clinical characteristics and challenges.

Corticotropin releasing factor-1 receptor antagonism associated with favorable outcomes of male reproductive health biochemical parameters.

Background: Disruption in androgen profiles and testicular adrenal rest tumors in males with congenital adrenal hyperplasia (CAH) can negatively affect sexual activity and fertility. Adrenal hyperandrogenism suppresses gonadotropin secretion and testicular adrenal rest tumors (TARTS), despite being noncancerous lesions, cause obstructive azoospermia and impaired testosterone (T) production. Circulating T in men with uncontrolled CAH is often predominantly adrenal in origin, which is reflected in high androstenedione/testosterone ratios (A4/T). Therefore, decreased luteinizing hormone (LH) levels and an increased A4/T are markers of impaired fertility in these individuals. Methods: Oral tildacerfont 200 to 1000 mg once daily (QD) (n=10) or 100 to 200 mg twice daily (n=9 and 7) for 2 weeks (Study 201), and 400 mg QD (n=11) for 12 weeks (Study 202). Outcomes measured changes from baseline in A4, T, A4/T, and LH. Results: Mean T levels increased in Study 201 from 375.5 ng/dL to 390.5 ng/dL at week 2 (n=9), 485.4 ng/dL at week 4 (n=4) and 420.7 ng/dL at week 6 (n=4). In Study 202, T levels fluctuated in the normal range from 448.4 ng/dL at baseline to 412.0 ng/dL at week 12. Mean LH levels increased in Study 201 from 0.68 IU/L to 1.59 IU/L at week 2 (n=10), 1.62 IU/L at week 4 (n=5) and 0.85 IU/L at week 6 (n=4). In Study 202, mean LH levels increased from 0.44 IU/L at baseline to 0.87 IU/L at week 12. Mean A4/T decreased across both studies. In Study 201, the mean A4/T changed from a baseline of 1.28 to 0.59 at week 2 (n=9), 0.87 at week 4 (n=4), and 1.03 at week 6 (n=4). In Study 202, the A4/T decreased from baseline of 2.44 to 0.68 at week 12. Four men were hypogonadal at baseline; all experienced improved A4/T and 3/4 (75%) reached levels <1. Conclusion: Tildacerfont treatment demonstrated clinically meaningful reductions in A4 levels, and A4/T with concomitant increased LH levels indicating increased testicular T production. The data suggests improvement in hypothalamic-pituitary-gonadal axis function, but more data is required to confirm favorable male reproductive health outcomes.

Impacts of algae supplements (Arthrospira & Chlorella) on growth, nutrient variables, intestinal efficacy, and antioxidants in New Zealand white rabbits.

An 8-week trial to examine the impacts of Arthrospira platensis and Chlorella vulgaris on the growth, nutrient aspects, intestinal efficacy, and antioxidants of 75 New Zealand white male rabbits (initial body weight = 665.93 ± 15.18 g). Herein the study was designed in one-way ANOVA to compare the effects of the two algae species with two levels of supplementations in the feeds of New Zealand white rabbits. The rabbits were divided into five groups (n = 15/group), where the first group was allocated as the control group (Ctrl) while the second and third groups received A. platensis at 300 or 500 mg/kg diet (Ap300 or Ap500). The fourth and fifth groups fed C. vulgaris at 300 or 500 mg/kg diet (Ch300 or Ch500). The basal diet rabbits exhibited the lowest values of weight, lipase, protease, and the highest feed conversion ratio, which improved noticeably with algae addition, particularly with Ap500, Ch300, and Ch500. All tested groups showed normal intestinal structure. Amylase potency, hematological indicators, and serum biochemistry revealed non-significant variation except for a higher serum total protein and lower total cholesterol in algal groups. The best GPx existed in groups fed algal diets, while favorable SOD and CAT efficiency occurred at the higher level of Arthrospira and both levels of Chlorella. In conclusion, incorporating Arthrospira or Chlorella in the diet of New Zealand white rabbits improved performance, nutrient utilization, intestinal efficacy, and antioxidants. Arthrospira (Ap500) and Chlorella (Ch300 or Ch500) have almost the same beneficial effect on rabbit performance.

Brentuximab-Induced Colitis in a Non-Stem-Cell Transplant Patient.

Many chemotherapeutic agents have been associated with drug-induced colitis (DIC). With newer agents' expansion of approval as first-line therapy for common cancers, it is important to be cognizant of their association with DIC. We present a case of brentuximab-associated DIC in an elderly woman with CD30+ Hodgkin lymphoma. Brentuximab's association with DIC was suspected by others in the literature, but a history of stem-cell transplant in them would blur the association with graft-vs-host disease. Lack of stem-cell transplant in our patient makes the link between brentuximab and DIC unambiguous.

Ameliorative impacts of sodium humate on heat-stressed laying Japanese quail (Coturnix coturnix Japonica).

A total of 300 laying Japanese quails (230.10 ± 20 g body weight) divided into four groups (15 birds in 5 replicates/group) were used to examine the impacts of dietary sodium humate (SH) supplementation at levels of 0% (control diet), 0.2%, 0.4% and 0.6% on egg variables and physiological merits of laying quails for 10 weeks under heat stress conditions (15 June and 23 August 2021). Results showed 0.4% SH increased (p < 0.05) weight (12.27 vs. 11.91 g), production (79.84% vs. 69.20%), mass (597.13 vs. 510.48 g) and brokenness (2.8% vs. 5.4%) of eggs as compared to control. Egg shape, shell thickness, shell strength and cholesterol content as well as feed conversion ratio were higher (80.2, 295.8 µm, 1.468 kg/cm,2 11.08 mg/g and 2.69, p < 0.05) in 0.4% SH than in control group (75.2, 279.0 µm, 1.304 kg/cm,2  14.94 mg/g and 2.76). Feed intake, percentages of eggs' shells, yolk, albumen and serum biochemistry (total protein, albumin, AST and HDL) were not altered with the dietary SH. Birds fed on SH diets showed higher levels of globulin, calcium and phosphorus, as well as lower contents of albumin/globulin ratio, triglycerides, cholesterol, corticosterone compared with the control. Regression analysis of antioxidants expected higher total antioxidant capacity (TAC), superoxide dismutase, glutathione peroxidase at 0.35%, and glutathione at 0.40% SH, while the lowest concentration of malondialdehyde was computed at 0.45%. Similarly, immunoglobulins (IgG and IgM) maximum values were determined at 0.35% and 0.40% levels. Moreover, the concentration of tumour necrosis factor-alpha increased (p < 0.05) in all SH levels as compared to the control group. It is conceivable to conclude that the dietary implementation of SH at a level of 0.4% improved egg variables and well-being aspects of laying quail exposed to heat stress conditions.

The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity.

Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29-100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.

Colonic Polypoid Vascular Ectasia in a Patient With Rectal Prolapse.

Vascular ectasia is a common cause of lower gastrointestinal (GI) bleeding in older patients. They typically present as flat or slightly raised fern-like bright red lesions. We report a rare case of a vascular ectasia presenting as a pedunculated polypoid lesion in a young patient with rectal prolapse. The pedunculated polyp was removed using hot snare polypectomy. This case highlights a unique presentation of a rare lesion and endoscopic management of these lesions.

FGF21 contributes to metabolic improvements elicited by combination therapy with exenatide and pioglitazone in patients with type 2 diabetes.

Fibroblast growth factor 21 (FGF21) is increased acutely by carbohydrate ingestion and is elevated in patients with type 2 diabetes (T2D). However, the physiological significance of increased FGF21 in humans remains largely unknown. We examined whether FGF21 contributed to the metabolic improvements observed following treatment of patients with T2D with either triple (metformin/pioglitazone/exenatide) or conventional (metformin/insulin/glipizide) therapy for 3 yr. Forty-six patients with T2D were randomized to receive either triple or conventional therapy to maintain HbA1c < 6.5%. A 2-h 75-g oral glucose tolerance test (OGTT) was performed at baseline and following 3 years of treatment to assess glucose tolerance, insulin sensitivity, and ß-cell function. Plasma total and bioactive FGF21 levels were quantitated before and during the OGTT at both visits. Patients in both treatment arms experienced significant improvements in glucose control, but insulin sensitivity and ß-cell function were markedly increased after triple therapy. At baseline, FGF21 levels were regulated acutely during the OGTT in both groups. After treatment, fasting total and bioactive FGF21 levels were significantly reduced in patients receiving triple therapy, but there was a relative increase in the proportion of bioactive FGF21 compared with that observed in conventionally treated subjects. Relative to baseline studies, triple therapy treatment also significantly modified FGF21 levels in response to a glucose load. These changes in circulating FGF21 were correlated with markers of improved glucose control and insulin sensitivity. Alterations in the plasma FGF21 profile may contribute to the beneficial metabolic effects of pioglitazone and exenatide in human patients with T2D.NEW & NOTEWORTHY In patients with T2D treated with a combination of metformin/pioglitazone/exenatide (triple therapy), we observed reduced total and bioactive plasma FGF21 levels and a relative increase in the proportion of circulating bioactive FGF21 compared with that in patients treated with metformin and sequential addition of glipizide and basal insulin glargine (conventional therapy). These data suggest that FGF21 may contribute, at least in part, to the glycemic benefits observed following combination therapy in patients with T2D.

Rare presentation of enoxaparin-induced skin necrosis in a postoperative patient.

Enoxaparin-induced skin necrosis is a rare complication of low-molecular weight heparin (LMWH) therapy. We describe a woman in her 50s who developed deep vein thrombosis (DVT), thrombocytopenia and necrotic skin lesions after initiation of enoxaparin for DVT prophylaxis. Despite high clinical suspicion of heparin-induced thrombocytopenia syndrome and a positive heparin-platelet factor 4 antibody, heparin serotonin assay was negative. This case emphasises the importance for clinical vigilance regarding complications to LMWH therapy.

Impacts of different antioxidants sources on semen quality and sperm fertilizing ability of Muscovy ducks under high ambient temperature.

The potentiality of coenzyme Q10 (CoQ10), D-Aspartic acids (D-Asp), Maca or vitamin C, as antioxidant agents, to reduce negative impacts of high ambient temperature on semen quality, oxidative capacity and fertility of Muscovy ducks was investigated. Seventy-five Muscovy males (34-wk of age) were distributed randomly into five experimental groups of fifteen ducks each. The first group was fed a basal diet without supplementation and served as a control. The other four groups were fed a basal diet supplemented with 400 mg CoQ10, 400 mg D-Asp, 500 mg Maca and 200 mg vitamin C (ascorbic acid) per kg diet for 17 consecutive weeks under high ambient temperature conditions. The dietary inclusion of antioxidants significantly maintains better semen variables and a higher fertility rate either for fresh or preserved semen. Among the tested antioxidants, the Maca group showed the best status and outperformed the others in terms of motility, viability, sperm cell concentration, intact acrosome and membrane integrity percentages, total proteins, total antioxidants capacity, glutathione peroxidase, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone, and the fertility rate for the fresh semen, as well as, forward motility, SOD and MDA for the preserved semen. The CoQ10 showed similar results to Maca in some measurements. Conversely, the basal diet had the poorest performance in all examined variables. The dietary incorporation of antioxidants (Maca or CoQ10) enhances fresh and preserved semen quantity and quality, as well as the fertility rate of Muscovy males under high ambient temperature conditions.

Perioperative Anxiolytic and Analgesic Effects of Pregabalin in Vitreo-Retinal Surgery: A Randomized, Double-blind Study.

OBJECTIVES: This study was done to examine the effect of a single, one-time pregabalin dose on postoperative pain, anxiety, and analgesic consumption after vitrectomy performed under the peribulbar block and to assess the satisfaction of the patients as well as the surgeons. METHODS: This randomized, double-blinded, placebo-controlled trial was conducted at Magrabi Eye, ENT and Dental Center, Doha, Qatar on 58 adult patients aged 37 - 75 years, who met status I and II of the American Society of Anesthesiologists (ASA) and scheduled for elective vitrectomy, under the peribulbar block (PB). Of the total participants, 30 cases were randomized to receive pregabalin, while the remaining received placebo 90 minutes before surgery. Pain was assessed using a Verbal Analog Scale (VAS) score, and the levels of anxiety were gauged by verbal anxiety score. RESULTS: Patients who received pregabalin had a significantly higher sedation score (3 ± 0 vs. & 2 ± 0.65; P < 0.05), and a significantly less anxiety score (3 ± 1.3 vs. 5 ± 1.6; P < 0.001) compared to the control group. During needle insertion for PB, patients in the pregabalin group experienced less pain compared to the control group (32 ± 15 vs. 44 ± 15; P < 0.05). Pregabalin group showed a significantly higher cooperation rate and patient satisfaction scores (3.2 ± 0.7 and 3.8 ± 0.4, respectively), compared to the placebo group (2.8 ± 0.7 and 3.4 ± 0.5, respectively). The placebo group required intraoperative midazolam more in comparison to the pregabalin group (19 vs. 5; P < 0.001). Moreover, the need for postoperative analgesia was more in the placebo group two hours postoperatively. CONCLUSIONS: Pregabalin is a potent premedication in controlling post-surgical pain and anxiety in patients undergoing vitrectomy under the PB.

Transcatheter Tricuspid Valve Intervention in Patients With Previous Left Valve Surgery.

BACKGROUND: Scarce data exist on patients with previous left valve surgery (PLVS) undergoing transcatheter tricuspid valve intervention (TTVI). This study sought to investigate the procedural and early outcomes in patients with PLVS undergoing TTVI. METHODS: This was a subanalysis of the multicenter TriValve registry including 462 patients, 82 (18%) with PLVS. Data were analyzed according to the presence of PLVS in the overall cohort and in a propensity score-matched population including 51 and 115 patients with and without PLVS, respectively. RESULTS: Patients with PLVS were younger (72 ± 10 vs 78 ± 9 years; p < 0.01) and more frequently female (67.1% vs 53.2%; P = 0.02). Similar rates of procedural success (PLVS 80.5%; no-PLVS 82.1%; P = 0.73), and 30-day mortality (PLVS 2.4%, no-PLVS 3.4%; P = 0.99) were observed. After matching, there were no significant differences in both all-cause rehospitalisation (PLVS 21.1%, no-PLVS 26.5%; P = 0.60) and all-cause mortality (PLVS 9.8%, no-PLVS 6.7%; P = 0.58). At last follow-up (median 6 [interquartile range 1-12] months after the procedure), most patients (81.8%) in the PLVS group were in NYHA functional class I-II (P = 0.12 vs no-PLVS group), and TR grade was ≤ 2 in 82.6% of patients (P = 0.096 vs no-PVLS group). A poorer right ventricular function and previous heart failure hospitalization determined increased risks of procedural failure and poorer outcomes at follow-up, respectively. CONCLUSIONS: In patients with PLVS, TTVI was associated with high rates of procedural success and low early mortality. However, about one-third of patients required rehospitalisation or died at midterm follow-up. These results would support TTVI as a reasonable alternative to redo surgery in patients with PLVS and suggest the importance of earlier treatment to improve clinical outcomes.

Dietary probiotics as a strategy for improving growth performance, intestinal efficacy, immunity, and antioxidant capacity of white Pekin ducks fed with different levels of CP.

The potential impacts of probiotics on the performance and health status of white Pekin ducks fed with optimal or suboptimal dietary CP were evaluated during the growing period. A total of 180 male white Pekin ducks (14-day-old ducks with an initial weight of 415.65 ± 2.20 g) were randomly divided into 4 experimental groups (45 in each group of 5 replicates) in a 2 × 2 factorial design. The main factors included 2 dietary CP levels (18 or 14%) and dietary probiotic addition (with or without probiotics). The probiotic source was supplemented at 0.2 g per kilogram of diet from a blend of Lactobacillus acidophilus and Lactobacillus casei. The results showed that the diet containing 18% CP and probiotics significantly increases the final and total weight gain. Activities of intestinal enzymes (amylase, lipase, and protease), morphometrics (villus length, goblet cell count, and cryptal depth), and carcass percentage were also increased significantly. Total protein content, lysozyme activity, bactericidal activity, nitro blue tetrazolium levels, alternative complement pathway, superoxide dismutase activity, and catalase activity were significantly increased, whereas glucose, cortisol, and total cholesterol levels were decreased when treated with diet containing 18% CP and probiotics. Conversely, the group treated with diet containing 14% CP without probiotics showed the poorest performance, carcass properties, immune response, and antioxidant potential. In conclusion, probiotic addition to the 14% CP diet improved the performance of white Pekin ducks caused by reduced CP diet to performance due to the 18% CP diet without probiotic supplementation.

Coincident remission of ankylosing spondylitis after autologous stem cell transplantation for multiple myeloma.

INTRODUCTION: Ankylosing spondylitis is an autoimmune disease with chronic inflammation of the spine and sacroiliac joints that is commonly treated with immunosuppressants including disease-modifying antirheumatic drugs and anti-tumor necrosis factor alpha therapy. CASE REPORT: A 75-year-old female with active ankylosing spondylitis on treatment with etanercept was referred to us for newly diagnosed IgG kappa free light chain multiple myeloma. After failing induction with revlimid, bortezomib, and dexamethasone, she was initiated on carfilzomib. Following the achievement of adequate response to induction, she underwent an autologous hematopoietic stem cell transplant selected for CD34+ cells with melphalan 200mg/m2 conditioning regimen. Given high-risk cytogenetics, i.e. monosomy 17 (17p) and hypodiploidy, she received two cycles of carfilzomib consolidation post-transplant. The patient tolerated the transplant well with successful engraftment and achieved complete remission of multiple myeloma with no detectable M spike, negative immunofixation study, and normalization of light chain ratio. While being off etanercept since the transplant, she noticed complete relief from joint pains related to her ankylosing spondylitis without a need to use the pain-relieving medications.Management and outcome: The patient has sustained remission of ankylosing spondylitis for two years post-transplant without flares or symptoms. She continues to remain off immunosuppressants. DISCUSSION: Although our patient had a coincident and unprecedented resolution of ankylosing spondylitis after receiving the hematopoietic stem cell transplant, this case consolidates the idea of transplant as a potential treatment option for ankylosing spondylitis and other rheumatological conditions.

The threshold for detecting a rise in airflow resistance during tidal breathing is lower in older patients with COPD than in healthy people of similar age.

INTRODUCTION: To investigate whether or not the threshold for subjectively detecting an increase in the resistance to airflow (LDT) during tidal breathing at rest rises in older age in patients with COPD, as it does in healthy people and asthmatics in remission. MATERIAL AND METHODS: We conducted an open cross-sectional study of 31 older patients (age 55-89) with COPD and 60 healthy volunteers (age 55-86). Inspiratory and expiratory resistive load detection thresholds (ILDT and ELDT respectively) and spirometry were measured. RESULTS: The mean (SD) ILDT was 5.93 (7.02) kPa.s/L in COPD patients, compared to 11.11 (8.47) in healthy people (P < 0.001) in the same age range. There was no significant correlation between ILDT and age in the COPD group (r = -0.182, P = 0.326), though significant correlation with age was found in healthy people (r = 0.591, P < 0.001). ILDT and ELDT in COPD patients correlated significantly with the FEV1/FVC ratio (r = 0.367, P = 0.048 and r = 0.481, P = 0.007 respectively) but not with other spirometry indices, height, weight, BMI, oxygen saturation or smoking pack-years. CONCLUSION: LDT during tidal breathing appears to be sensitized, and thereby lower, in older COPD patients, possibly due to altered central regulation of the threshold or as a consequence of the effect lung compliance, recoil and volume changes have on afferent input from mechano-receptors in COPD. Older COPD patients with good cognition are therefore likely to be as aware of changing airways resistance as younger patients and take appropriate therapeutic action.

McCune-Albright syndrome and type 1 diabetes mellitus: a novel presentation.

McCune-Albright syndrome (MAS) is caused by postzygotic somatic activating mutations of GNAS and is classically characterized by the clinical triad of peripheral precocious puberty, café-au-lait pigmentation, and polyostotic fibrous dysplasia. It can also present with other hyperfunctioning endocrinopathies, including growth hormone excess, hyperprolactinemia, hypercortisolemia, hyperthyroidism, and renal phosphate wasting due to excess fibroblast growth factor 23. We review the clinical, biochemical, radiological, and genetic findings in a 7-year-old girl diagnosed with MAS at age 4 and then with autoimmune type 1 diabetes mellitus at age 7. While MAS is associated with hyperglycemia secondary to growth hormone excess and hypercortisolemia, an association with diabetes mellitus has not been demonstrated. We review the unique presentation of a patient with these two rare conditions.

Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus.

We examined if urinary angiotensinogen (uAOG), a marker of intrarenal renin-angiotensin system activity, antedates stage 3 chronic kidney disease (CKD) using samples from participants in the Diabetes Control and Complications Trial (DCCT) and later in the Epidemiology of Diabetes Intervention and Complications (EDIC) trial. In a nested case-control design, cases were matched at the outcome visit (eGFR less than 60, 21-59 mL/min per 1.73 m2 ) on age, gender, and diabetes duration, with controls: eGFR (95, 75-119, mL/min per 1.73 m2 .) Additionally, in an exploratory analysis progressive renal decline (PRD), defined as eGFR loss >3.5 mL/min per 1.73m2 /year, was evaluated using only data from EDIC because no progressions were observed during DCCT. At the EDIC visit, which antedated the GFR outcome visit by 2 years (range 1-7years) the median uAOG/creatinine was markedly higher in cases than in controls (13.9 vs. 3.8 ng/mg P = 0.003) whereas at the DCCT visit, which antedated the GFR outcome by 17 to 20 years it was not (2.75 vs. 3.16 ng/mg, respectively). The Odds Ratio for uAOG and CKD stage 3 development was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 1.82 (1.00-3.29) but no longer significant when Albumin Excretion Ratio (AER) was included 1.21 (0.65-2.24).In the PRD analysis, uAOG/creatinine was sixfold higher in participants who experienced PRD than in those who did not (26 vs. 4.0 ng/mg, P = 0.003). The Odds Ratio for uAOG and PRD was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 2.48 (1.46-4.22) but no longer significant when AER was included 1.32 (0.76-2.30). In people with type1 diabetes, a robust increase in uAOG antedates the development of stage 3 CKD but is not superior to AER in predicting this renal outcome. Increased uAOG moreover is associated with PRD, an index of progression to End Stage Kidney Disease (ESKD).

Long-term outcomes by response to neoadjuvant chemotherapy or chemoradiation in patients with resected pancreatic adenocarcinoma.

BACKGROUND: Response of pancreatic adenocarcinoma to neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) may be associated with prognosis, but long-term outcomes based on response to neoadjuvant therapy have not been well evaluated to date. METHODS: The National Cancer Database was queried for patients with pancreatic adenocarcinoma receiving nCT/nCRT. To evaluate response to nCT/nCRT, comparisons were made from cT and cN stage to the respective post-neoadjuvant therapy ypT and ypN stages. Based on these comparisons, patients were classified as responders, progressors, or non-responders. Statistical analyses included estimation of survival using Kaplan-Meier analysis, as well as multivariable Cox proportional hazards modeling. RESULTS: Of 2,028 patients, 30% had a response, 32% progressed, and 38% had no response; 1% of patients experienced pathologic complete response (pCR). Responders were more likely to have received multi-agent chemotherapy (P=0.0001) as well as radiotherapy (RT) (P=0.02) in the neoadjuvant setting. Response to nCT/nCRT was also associated with a higher R0 resection rate (P=0.02). At a median follow-up of 49 months, median overall survival (OS) was higher in responders than non-responders or progressors (29.9 vs. 24.3 vs. 22.2 months, P<0.001). The mean OS for patients experiencing pCR was 55.5 months. On multivariable analysis, treatment response was independently associated with OS (P=0.02). CONCLUSIONS: Response to nCT/nCRT independently predicts long-term outcomes following resection of pancreatic adenocarcinoma; higher rates of treatment response were observed for patients receiving neoadjuvant RT as well as neoadjuvant multi-agent chemotherapy. These results may have implications on strategies to improve response rates.