Update on the use of bisphosphonates in the management of postmenopausal osteoporosis by obstetricians-gynecologists

Obstetricians-gynecologists often have a special and long-term relationship with their patients and are ideally placed to assess their fracture risk and to institute appropriate therapy for osteoporosis. Assessment of risk factors according to the World Health Organization and more recent guidelines (e.g., age, smoking history, previous fracture, parental fracture, corticosteroid use, weight) enables the clinician to target patients for testing of bone mineral density by techniques such as dual-energy x-ray absorptiometry at the proximal femur. The current therapy of choice is an oral bisphosphonate, which has proven efficacy in increasing bone mineral density, reducing bone-turnover markers, and reducing fracture rates. Their main drawback is inconvenient dosing requirements, which necessitates taking the drug in the morning at least 30 minutes before the first meal or drink of the day; this may contribute to poor adherence with therapy and suboptimal outcomes. The availability of daily or weekly (alendronate and risedronate) or monthly (ibandronate) bisphosphonates means that patients can have therapy at their preferred frequency, and along with education regarding lifestyle issues such as nutrition, exercise, smoking, and alcohol use, and measures to reduce tripping in the home, should reduce the prevalence of osteoporotic fractures. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall that there are high-risk fracture patients, explain that Ob/Gyn physicians should target their diagnostic and treatment options to these patients, and state that there are ways that increase compliance to recommended bisphosphonates in addition to the recommended lifestyle changes.     

Physician referral patterns for stutterers

Many children who stutter initially seek guidance from their pediatricians. Pediatricians often do not refer stutterers for speech therapy. We present a brief analysis of pediatricians' views regarding stuttering, as well as their exposure to patients who stutter. We present a practical approach to children who stutter.     

The mathematical modelling of the displacement of the hard palate tissues in conservative uranoplasty

Presents a mathematical model of sparing uranoplasty techniques developed by the authors; using this model, a physician may assess before surgery the volume of tissues needed to close the palatal defect. Experience gained with 72 surgeries carried out in children with unilateral cleft palate confirms the desirability of preliminary computations. Mathematical models for the most prevalent sparing uranoplasty methods are offered.     

Oral contraceptives and cardiovascular risk. Taking a safe course of action

Although a prospective, longitudinal study on the long-term cardiovascular effects of oral contraceptives has yet to be performed, available data are useful in determining a safe course of action while physicians await definitive answers. Exogenous sex steroids produce important effects on lipid metabolism. Early intervention against cholesterol is important in reducing cardiovascular risk. Current users of high-dose formulations, particularly older women who smoke, are at greatest risk for cardiovascular complications, especially myocardial infarction. Low-dose oral contraceptives have more modest effects on lipid metabolism, but important differences in the potency of progestins remain. Fortunately, recent studies among users of lower-dose oral contraceptive formulations fail to show an increase in cardiovascular morbidity and mortality. Nonetheless, prudent physicians will avoid oral contraceptives that may adversely affect lipoprotein metabolism, such as those containing progestins with high androgenic and antiestrogenic potency.     

Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma

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A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia

Iron deficiency anemia (IDA) is common in many chronic diseases, and intravenous (IV) iron offers a rapid and efficient iron correction. This trial compared the efficacy and safety of iron isomaltoside and iron sucrose in patients with IDA who were intolerant of, or unresponsive to, oral iron. The trial was an open‐label, comparative, multi‐center trial. Five hundred and eleven patients with IDA from different causes were randomized 2:1 to iron isomaltoside or iron sucrose and followed for 5 weeks. The cumulative dose of iron isomaltoside was based on body weight and hemoglobin (Hb), administered as either a 1000 mg infusion over more than 15 minutes or 500 mg injection over 2 minutes. The cumulative dose of iron sucrose was calculated according to Ganzoni and administered as repeated 200 mg infusions over 30 minutes. The mean cumulative dose of iron isomaltoside was 1640.2 (standard deviation (SD): 357.6) mg and of iron sucrose 1127.9 (SD: 343.3) mg. The primary endpoint was the proportion of patients with a Hb increase ≥2 g/dL from baseline at any time between weeks 1‐5. Both non‐inferiority and superiority were confirmed for the primary endpoint, and a shorter time to Hb increase ≥2 g/dL was observed with iron isomaltoside. For all biochemical efficacy parameters, faster and/or greater improvements were found with iron isomaltoside. Both treatments were well tolerated; 0.6% experienced a serious adverse drug reaction. Iron isomaltoside was more effective than iron sucrose in achieving a rapid improvement in Hb. Furthermore, iron isomaltoside has an advantage over iron sucrose in allowing higher cumulative dosing in fewer administrations. Both treatments were well tolerated in a broad population with IDA.     

Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study

Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 10⁶ CD34⁺ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 10⁶ CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 10⁶ CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation.     

An Exploratory Study on Resistance Spot Welding of Titanium Alloy Ti-6Al-4V

Resistance spot welding (RSW) is one of the most effective welding methods for titanium alloys, in particular Ti-6Al-4V. Ti-6Al-4V is one of the most used materials with its good ductility, high strength, weldability, corrosion resistance, and heat resistance. RSW and Ti-6Al-4V materials are often widely used in industrial manufacturing, particularly in automotive and aerospace industries. To understand the phenomenon of resistance spot weld quality, the physical and mechanical properties of Ti-6Al-4V spot weld are essential to be analyzed. In this study, an experiment was conducted using the Taguchi L9 method to find out the optimum level of the weld joint strength. The given optimum level sample was analyzed to study the most significant affecting RSW parameter, the failure mode, the weld nugget microstructure, and hardness values. The high heat input significantly affect the weld nugget temperature to reach and beyond the β-transus temperature. It led to an increase in the weld nugget diameter and the indentation depth. The expulsion appeared in the high heat input and decreased the weld nugget strength. It was caused by the molten material ejection in the fusion zone. The combination of high heat input and rapid air cooling at room temperature generated a martensite microstructure in the fusion zone. It increased the hardness, strength, and brittleness but decreased the ductility.     

Multiple Myeloma in Hispanics: Incidence,Characteristics, Survival,Results of Discovery,and Validation Using Real-World and Connect MM Registry Data

BackgroundMultiple myeloma (MM) in Hispanics has never been studied. We therefore sought to determine the clinical characteristics and overall survival in MM of Hispanics compared to non-Hispanic whites (NHW) and non-Hispanic blacks (NHB).Patients and MethodsA single-center analysis of 939 patients diagnosed with MM from 2000 to 2017 with a large representation of NHB (n = 489), Hispanics (n = 281), and NHW (n = 169) was conducted to evaluate outcomes and disease characteristics. We used the Connect MM Registry, a large US multicenter prospective observational study with newly diagnosed MM patients, as a validation cohort.ResultsHispanics had a higher incidence of MM compared to NHW. The median age at presentation was 5 years younger (median, 65 years) in Hispanics compared to NHW (median, 70 years), and patients were more likely to present with renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Hispanics had a higher proportion of Revised International Staging System (R-ISS) stage I disease compared to NHW and NHB (P = .03), while there was no difference in cytogenetics between Hispanics and NHB/NHW. In the multivariate analysis, only high-risk disease and response to first-line therapy significantly affected survival.ConclusionIn this first and largest analysis of MM in Hispanics, we found that Hispanics present at a younger age, have a higher incidence of renal dysfunction, and have low R-ISS stage disease at presentation. With equal access to therapy, Hispanics have survival similar to NHW/NHB.