Health-related quality of life (HRQoL) from HIV patients' perspective: comparison of patient-reported outcome (PRO) measures among people living with hiv (PLWH) and other chronic clinical conditions.

BACKGROUND: People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient's reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies. METHODS: A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs. RESULTS: 230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy. CONCLUSIONS: In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice.

Diabetes and severity of COVID-19: What is the link?

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

The role of gut microbiota in mediating obesity and diabetes mellitus.

OBJECTIVE: This review inspects the relations between the microbiota and the intestinal immune system in the advancement of metabolic illnesses, such as obesity and diabetes mellitus. The role of the microbiota in intestinal immune defense and the control of metabolism are subject to examination. MATERIALS AND METHODS: In type 1 diabetes, the adhesion proteins prompt inside the intestinal epithelium prompt a more significant immune response that may result in the destruction of pancreatic ß cells by CD8+ T-lymphocytes, as well as increased articulation of interleukin-17, which is associated with autoimmunity. Studies suggest that the beginning of metabolic ailments and certain co-morbidities can be viewed in light of the protection between the gut microbiota and the intestinal immune system. The gut microbiota is analyzed as a key regulator of metabolic ailments. Research demonstrates that obese patients with type 2 diabetes have a certain gut microbiota and that the microbiota is translocated from the gut to the tissues in conjunction with the illness, which instigates inflammation. RESULTS: Research in animals and people suggests that a probiotic supplement may regulate the gut microbiota, thereby improving the prognosis for diabetes. CONCLUSIONS: The mechanism underlying this phenomenon relates to a decrease in the inflammatory reaction and oxidative stress, as well as a decrease in leaky gut. Such reactions increase insulin sensitivity and reduce autoimmune responses.

Diabetic foot infections: a comprehensive overview.

Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.

Gestational weight gain as an independent risk factor for adverse pregnancy outcomes in women with gestational diabetes.

OBJECTIVE: Obesity and gestational diabetes mellitus (GDM) are rising worldwide. This study retrospectively evaluated the role of excessive gestational weight gain (eGWG) in women with GDM and different pre-pregnancy body mass indices (BMIs). PATIENTS AND METHODS: Optimal glycaemic control was defined as achieving glucose target thresholds in more than 80% of measurements. 283 women with GDM were categorized as underweight, normal weight, overweight or obese based on WHO's classification scheme. eGWG was defined as >18.0 kilograms for women who were underweight, >15.8 kilograms for those who were normal weight, >11.3 kilograms for those who were overweight and >9.0 kilograms for those who were obese. For the analysis, women were divided into two groups: normal and excessive GWG. The main outcomes measured were incidences of large/small for gestational age (LGA/SGA), macrosomia, preterm delivery, hypertensive disorders and caesarean sections (CS). RESULTS: Excessive GWG was associated with higher birth weight and percentile (p<0.001), and with a higher prevalence of LGA (p<0.001), macrosomia (p=0.002) and hypertensive disorders (p=0.036). No statistical differences were found for the week of delivery, or prevalence of CS and SGA. The multivariate analysis highlighted both pre-pregnant BMI and eGWG as independent risk factors for LGA and macrosomia. Women with a pre-pregnant BMI of at least 25 and eGWG have a 5.43-fold greater risk of developing LGA (p=0.005). CONCLUSIONS: When combined with an inadequate pre-pregnant BMI, eGWG acts as a "synergic risk factor" for a poor outcome. When obesity or GDM occur, an optimal GWG can guarantee a better pregnancy outcome.

Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients.

INTRODUCTION: Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. SUBJECTS AND METHODS: A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. RESULTS: Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24-0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. CONCLUSION: This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.

Understanding the effect of acromegaly on the human skeleton.

INTRODUCTION: Acromegaly, caused in most cases by Growth Hormone (GH)-secreting pituitary adenomas, is characterized by increased skeletal growth and enlargement of the soft tissue, because GH and its effector Insulin-like Growth factor-1 are important regulators of bone homeostasis and have a central role in the longitudinal bone growth and maintenance of bone mass. Areas covered: Despite the anabolic effect of these hormones is well known, as a result of the stimulation of bone turnover and especially of bone formation, many acromegalic patients are suffering from a form of secondary osteoporosis with increased risk of fractures. Expert commentary: In this review, we summarize the pathophysiology, diagnosis, clinical picture, disease course and management of skeletal complications of acromegaly, focusing in particular on secondary osteoporosis and fracture risk in acromegaly.

Further vitamin D analogs.

In this brief review we point out the specificities of the vitamin D system that are necessary to understand why each change in the molecule can result in significantly different biologic effects. Vitamin D, with a specific receptor in most of the tissues, has innumerable potential therapeutic applications in many clinical fields. However, excessive pharmacologic increments of circulating natural metabolites carry the risk of significant side effects. To avoid this, natural vitamin D molecules have been modified to more selectively stimulate some tissues. Changes have been attempted on particular parts of the molecule in order to affect some specific step of the complex machinery that characterize the vitamin D system. The first modifications were those in the side chain of the molecule, which are expected to affect, either or both, the steps of binding to transfer protein or the interaction with catabolic enzymes. More recently other regions, like A-ring (involved with receptor interaction) or CD bicyclic ring (involved with molecule stability), have been modified to obtain always more selective products. Notably each modification of the molecule also affects its shape thus further and variably modifying its interaction with the VDR, with the transport proteins or the catabolic enzymes. As a consequence, the biologic effects of new molecules become less predictable and require in vitro evaluation, experimental animal studies and a complete and specific clinical validation in specific disease states. With thousands of analogs synthesized in the laboratories, only a minority are approved for clinical employment. Besides secondary hyperparathyroidism and osteoporosis, Vitamin D analogs can be employed in other clinical conditions like cancer and autoimmunity diseases. We briefly report on some new experimental or already approved analogs in their main clinical fields of employment.

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

[Pathophysiology of secondary hyperparathyroidism: the role of FGF23 and Klotho]. / Fisiopatologia dell'iperparatiroidismo secondario: ruolo di FGF23 e Klotho.

Secondary hyperparathyroidism is a complex metabolic alteration secondary to chronic kidney disease (CKD). Reduction of 1,25(OH)2D3 synthesis is the first derangement, followed by an increase in PTH, and, lastly, calcium and phosphate modifications. Vitamin D is a hormone whose actions take place through a specific receptor, the vitamin D receptor (VDR), which is ubiquitous. Accordingly, heterogeneous biological effects can be added to the classical effects on mineral bone metabolism. In the pathophysiology of secondary hyperparathyroidism, an important role is also played by alterations of calcium transport, which is under the control of two receptors: VDR and CaSR (calcium-sensing receptor). The expression of these receptors is reduced during CKD. Recent findings have allowed to identify a new hormonal system, the FGF23-Klotho axis, that integrates the old and simple, but now inadequate, PTH-Vit D axis. FGF23 is a circulating factor produced by osteocytes that inhibits renal phosphate reabsorption and 1-alpha-hydroxylase activity. As such, FGF23 is involved in phosphate homeostasis and its serum levels increase along with the progression of CKD. Interestingly, FGF23 has very low affinity for its receptor and requires the activity of Klotho, an anti-aging gene, to become active. These new actors allow us to identify a bone-kidney axis, whose real physiological importance is still under evaluation.

[Gastrointestinal opportunistic infections and human immunodeficiency virus (HIV). Case report]. / Infezioni opprtuniste gastrointestinali e HIV. Caso clinico.

There have been millions of people found to have AIDS. Death rates from AIDS have declined 15% to 20% in the past 5 years. However, nearly 75000 people will die with AIDS in this year. Patients with AIDS are also at risk for developing both Aids-defining cancers, such as Kaposi's sarcoma and non-Hodgkin lymphoma, and non-Aids-defining cancers and opportunistic infections. In patients with advanced Aids, the Cytomegalovirus is a frequent cause of chorioretinitis, pneumonitis, chronic perineal ulcerations and oesophagitis. It has been involved in endocrine, bone marrow, central nervous system and kidney abnormalities. CMV infection of the small bowel accounts for only 4.3% of all cytomegalovirus infection of the GI tract (large bowel 47%, duodenum 21,7%, stomach 17,4%); isolated cases of small bowel perforation due to CMV have been reported in AIDS patients, and all but one patient died. The Authors report a rare case of an HIV-positive young man with gastroenteric Cytomegalovirus infection responsible for generalized peritonitis from multiple perforations.