Use of Tirzepatide in Adults with Type 2 Diabetes Mellitus: Scientific Evidence and Practical Aspects.

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.

Giant Condyloma Acuminata (Buschke-Lowenstein Tumor): Review of an Unusual Disease and Difficult to Manage.

Giant condyloma acuminatum (GCA) or Buschke-Loewenstein tumor is a rare disease, with an estimated prevalence of 0.1%. It was initially described in 1896 by Buschke and later in 1925 by Buschke and Loewenstein. Classic condyloma acuminata (CCA) and squamous cell carcinoma (SCC) were initially described as different entities. These three entities are currently considered to correspond to the same spectrum of different but not exclusive malignant transformations, associated with multiple risk factors such infection by human papilloma virus (HPV), immunodeficiencies, poor hygiene, multiple sexual partners, and chronic genital infections. HPV subtypes 6 and 11 are associated with 90% of GCA. It presents as a cauliflower-like tumor in the genital region with bad odor, bleeding, and local infection, differential diagnosis with multiple conditions should be considered, and sexually transmitted diseases should always be investigated. GCA has a higher rate of malignant transformation than CCA and tends to infiltrate adjacent soft tissues. The therapeutic approach is controversial but is considered that the resection with free edges is the gold standard and can be combined with adjuncts. The recurrence rate is high. Overall mortality is 21% and is associated with morbidity caused by recurrences. Imiquimod cream 5% has recently shown good results as monotherapy and in combination with ablative and surgical treatments. The quality of life is diminished in patients with this condition. In this review, we address the different aspects of this rare entity including the therapeutic approach.

Catalase but not vitamin D receptor gene polymorphisms are associated with nonsegmental vitiligo in Northwestern Mexicans.

BACKGROUND: Vitiligo is an acquired pigmentation disorder characterized by melanocyte loss via autoimmune mechanisms triggered by oxidative stress. Gene polymorphisms in antioxidant enzymes and immunomodulators such as catalase (CAT) and vitamin D receptor (VDR), respectively, have been linked to vitiligo in European and Asian populations. Our aim was to evaluate the role of CAT and VDR gene polymorphisms as well as CAT and vitamin D in nonsegmental vitiligo in Northwestern Mexicans. METHODS: A total of 357 subjects, 173 nonsegmental vitiligo patients and 184 age-gender matched healthy controls, were genotyped by PCR-restriction fragment length polymorphism. CAT activity was determined in 39 patients and in 39 controls and vitamin D (VitD) levels in 35 individuals per group. RESULTS: CAT 419 C/T gene polymorphism was not informative, -89 A/T was associated with risk (P = 0.02), and 389 C/T conferred protection against vitiligo along with AT haplotype (P < 0.01 in both cases). VDR BsmI, ApaI, and TaqI gene polymorphisms were not associated with vitiligo, but BsmI was more prevalent in patients with Koebner phenomenon (P = 0.02). Serum CAT activity and VitD levels were lower in patients than in controls, but they showed no association with any vitiligo clinical characteristics neither with their gene polymorphisms. CONCLUSIONS: Our results suggest a role for CAT gene polymorphisms in vitiligo susceptibility in the Mexican population and a lack of association with VDR gene polymorphisms.

Real-Time Decentralized Neural Control via Backstepping for a Robotic Arm Powered by Industrial Servomotors.

This paper presents a continuous-time decentralized neural control scheme for trajectory tracking of a two degrees of freedom direct drive vertical robotic arm. A decentralized recurrent high-order neural network (RHONN) structure is proposed to identify online, in a series-parallel configuration and using the filtered error learning law, the dynamics of the plant. Based on the RHONN subsystems, a local neural controller is derived via backstepping approach. The effectiveness of the decentralized neural controller is validated on a robotic arm platform, of our own design and unknown parameters, which uses industrial servomotors to drive the joints.

Impact of frailty in older patients with diabetes mellitus: An overview.

Diabetes and frailty are two conditions that frequently occur concurrently and are increasingly prevalent in the older patient. We review the concept, epidemiology and consequences of frailty, and the implications of the presence of frailty in the management of diabetes. Frailty is associated with decreased quality of life, a risk of falls, new or increased disability, hospitalization, and increased mortality. All of these factors affect the management of diabetes in older patients. It is important to rule out frailty in all diabetic patients aged >70 years; if frailty is suspected, a comprehensive and multidisciplinary medical and functional assessment of the patient should be conducted to develop an individualized treatment plan. This plan should include nutritional measures, physical activity, and education on self-care and diabetes; drugs should not be used without a clear indication. Antihyperglycemic drugs that may cause excessive weight loss and/or are associated with a high risk of hypoglycemia should be avoided.

Relationships between obesity, glycemic control, and cardiovascular risk factors: a pooled analysis of cross-sectional data from Spanish patients with type 2 diabetes in the preinsulin stage.

BACKGROUND: Obesity is associated with the onset of type 2 diabetes mellitus (T2D), but reports conflict regarding the association between obesity and macrovascular complications. In this study, we investigated associations between cardiovascular risk factors and body mass index (BMI) and glycemic control in non-insulin-treated patients with T2D. METHODS: Authors gathered cross-sectional data from five observational studies performed in Spain. Generalized logit models were used to analyze the relationship between cardiovascular risk factors (independent variables) and 5 BMI strata (<25 kg/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2, ≥40 kg/m2) and 5 glycated hemoglobin (HbA1c) strata (≤6.5%, >6.5-7%, >7-8%, >8-9%, >9%) (dependent outcomes). RESULTS: In total, data from 6442 patients were analyzed. Patients generally had mean values of investigated cardiovascular risk factors outside recommended thresholds. Younger patients had higher BMI, triglyceride levels and HbA1c than their older counterparts. Diastolic blood pressure, systolic blood pressure and triglyceride levels were directly correlated with BMI strata, whereas an inverse correlation was observed between BMI strata and high-density lipoprotein cholesterol (HDL-C) levels, patient age, and duration of T2D. Increased duration of T2D and total cholesterol levels, and decreased HDL-C levels were associated with a higher HbA1c category. BMI and HbA1c levels were not associated with each other. CONCLUSIONS: As insulin-naïve patients with T2D became more obese, cardiovascular risk factors became more pronounced. Higher BMI was associated with younger age and shorter duration of T2D, consistent with the notion that obesity at an early age may be key to the current T2D epidemic. Glycemic control was independent of BMI but associated with abnormal lipid levels. Further efforts should be done to improve modifiable cardiovascular risk factors.

Sensitivity study to evaluate the dosimetric impact of off-axis ratio profiles misalignment on TomoTherapy second dose validation.

Accurate dose planning and delivery are very important in the intensity modulated radiation therapy. For helical TomoTherapy dose validation, a TomoTherapy second check software, called MU-Tomo, has been developed using archived patient documents, initial coordinates and planned dose of the point of calculation, and common dosimetric functions. Based on this software, sensitivity studies on 50 patient cases have been evaluated to show the impact of off-axis ratio profile misalignment on point dose calculation. Off-axis ratio is defined as the dose profile normalized to its maximum dose value. Sensitivity studies were done for three scenarios: oscillating the fluctuation regions of two off-axis profiles, shifting the profiles, and rotating the profiles. The result of the oscillation trial is linear along the change of longitudinal off-axis ratio (OARy), while oscillating the lateral off-axis ratio (OARx) has little influence on the dose calculation. For shifting, the variation in the percentage difference from the non-shifting value is about 15 times larger in OARy modification than in OARx modification. Rotating OARx by +/- 6' gave less than 1.5% +/- 0.20% difference compared to the non-rotating value. Rotating OARy by +/- 1' changes the result more than 5% +/- 2.69%. Therefore, for helical TomoTherapy dose validation, commissioned OARy profiles are more sensitive than OARx to oscillation, shifting and rotating. As a result, different tolerances for OARx and OARy may be required for annual quality assurance.

Mineral metabolism in obese patients following vertical banded gastroplasty.

BACKGROUND: Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation. METHODS: Sixteen morbidly obese patients (14 women, 2 men) with a mean (+/-SD) age of 38 +/- 9 years and a body mass index (BMI) of 47.1 +/- 8.1 kg/m2 were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss. RESULTS: Mean weight loss was 28 +/- 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery. CONCLUSIONS: Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.

Percutaneous treatment of transplant renal artery stenosis in children.

Percutaneous treatment of renal artery stenosis (RAS) is an accepted procedure and numerous reports have been published. However, experience with its use in RAS in the transplanted kidney in children is scarce. Since 1994 we have diagnosed RAS in seven children with the use of Doppler ultrasonography (US), confirming it with percutaneous angiography (PAG). In six of the seven patients percutaneous transluminal angioplasty (PTA) was performed. In one patient a metallic stent was placed due to the extension of the arterial lesion, and a second stent was placed in another child when a re-stenosis was diagnosed 1 month after the PTA. All patients presented with hypertension (de novo or 30% increase over previous values). After ruling out acute rejection, calcineurin inhibitor toxicity, and urinary obstruction, US was performed and, when an increase in arterial flux velocity was registered, PAG was also performed. Six children showed an increase in serum creatinine (Cr) and proteinuria. Blood pressure decreased after the procedure and Cr returned to previous levels in all children. One of the grafts was lost due to chronic transplant rejection 7 years later. The other children have a functioning kidney. Although this is a small group of patients, the consistently good results and the lack of reported experience prompted us to communicate our preliminary observation.

Argon laser photocoagulation for chronic clinically significant cystoid macular edema

We report the therapeutic outcome of 14 eyes of 11 patients with chronic clinically significant pseudophakic cystoid macular edema refractory to medical management who underwent argon laser photocoagulation of the perifoveal area. Inclusion criteria included chronic cystoid macular edema of more than six months duration of decreased visual acuity (20/100 or less), positive fluorescein angiogram and contact lens examination, pseudophakos with posterior chamber intraocular lens and intact posterior capsule, normal fasting blood sugar, failed medical treatment and minimal follow up of six months. Fifty per cent of the eyes improved after laser treatment (p = .0345, relative to unchanged plus worsened cases). Further prospective, randomized, clinical trials are recommended to define the effectiveness of this treatment protocol

Antibodies to lens crystallins after endocapsular cataract surgery

Levels of serum antibodies against lens alpha, beta H and beta L crystallins were determined in 15 patients before and after endocapsular cataract extraction. The most abundant antibody at the time of surgery was anti-beta L, followed by anti-beta H and anti-alpha. An increase in the basal levels of these antibodies was seen after surgery in 93 percent of the cases. Relative increase was highest for anti-alpha, followed by anti-beta H and anti-beta L. There were individual variations both in the shape of the time-dependent antibody response after surgery and in the relative intensity of the response to the different antigens. The endocapsular technique therefore leads to the release of crystallins into the anterior chamber in sufficient amounts to provoke in many patients a humoral immune response

Faco ®smallport® / Phaco-small story

The smallport system is a new technology that brings to surgeons who begin in phacoemulsification more advantages and control in surgery, more security and less time required for learning. The authors show the differences (advantages and disadvantages) between standard systems and the endocapsular ®smallport®. In nuclei up to grade 3 hardness we have good results with low phaco power (5-10 per cent ) and higher linear aspiration (200 mmHg) causing minimal loss of endothelial cells and quick visual rehabilitation

Surgically induced astigmatism. A comparison of different cataract incisions and closures

A single center, single surgeon, nonrandomized, prospective clinical trial was performed comparing the keratometric induced astigmatism by different types of incisions and closures, one day, one week, one month and three months after 255 cataract surgeries. After phacoemulsification, or in rare cases after extracapsular cataract extraction, through a scleral pocket or limbal incision, patients received either a 5 x 6 mm, 5.5 mm, or 6 mm diameter polymethylmethacrylate optic posterior chamber intraocular lens. Incision was closed with either none, one horizontal or radial, or running 10-0 nylon suture. Vector analysis calculations of prism diopters of mean postoperative-induced keratometric astigmatism showed a trend to lesser values at each interval in scleral pocket incisions but statistically significant difference only at 1 day and 1 week between 9-mm and 6-mm limbal, and 5-mm and 6-mm scleral pocket incisions. Other subgroup analyses, including incision shape and distance from limbus, and type of suture, did not reach statistical significance. Horizontal, 5-mm, sutureless scleral tunnel incision showed less induced astigmatism with more rapid stable refraction