Identifying determinants for falls among Iranian older adults: insights from the Bushehr Elderly Health Program.

BACKGROUND: Falls are a common cause of fractures in older adults. This study aimed to investigate the factors associated with spontaneous falls among people aged ≥ 60 years in southern Iran. METHODS: The baseline data of 2,426 samples from the second stage of the first phase of a prospective cohort, the Bushehr Elderly Health (BEH) program, were included in the analysis. A history of spontaneous falls in the year before recruitment was measured by self-report using a standardized questionnaire. Demographic characteristics, as well as a history of osteoarthritis, rheumatoid arthritis, low back pain, Alzheimer's disease, epilepsy, depression, and cancer, were measured using standardized questionnaires. A tandem gait (heel-to-toe) exam, as well as laboratory tests, were performed under standard conditions. A multiple logistic regression model was used in the analysis and fitted backwardly using the Hosmer and Lemeshow approach. RESULTS: The mean (standard deviation) age of the participants was 69.34 (6.4) years, and 51.9% of the participants were women. A total of 260 (10.7%, 95% CI (9.5-12.0)%) participants reported a spontaneous fall in the year before recruitment. Adjusted for potential confounders, epilepsy (OR = 4.31), cancer (OR = 2.73), depression (OR = 1.81), low back pain (OR = 1.79), and osteoarthritis (OR = 1.49) increased the risk of falls in older adults, while the ability to stand ≥ 10 s in the tandem gait exam (OR = 0.49), being male (OR = 0.60), engaging in physical activity (OR = 0.69), and having high serum triglyceride levels (OR = 0.72) reduced the risk of falls. CONCLUSION: The presence of underlying diseases, combined with other risk factors, is significantly associated with an increased risk of falls among older adults. Given the relatively high prevalence of falls in this population, it is crucial to pay special attention to identifying and addressing these risk factors.

Examining the immunological responses to COVID-19 vaccination in multiple myeloma patients: a systematic review and meta-analysis.

BACKGROUND: Impaired immune response in multiple myeloma renders the patients vulnerable to infections, such as COVID-19, and may cause worse response to vaccines. Researchers should analyze this issue to enable the planning for special preventive measures, such as increased booster doses. Therefore, this meta-analysis aimed to evaluate the response and efficacy of COVID-19 vaccines in patients with multiple myeloma. METHODS: This meta-analysis followed PRISMA 2020 guidelines, conducting a comprehensive database search using specified keywords. Study selection involved a two-phase title/abstract and full-text screening process. Data extraction was performed by two researchers, and statistical analysis involved meta-analysis, subgroup analysis based on vaccine dosage and study time, random effects meta-regression, and heterogeneity testing using the Q test. RESULTS: The meta-analysis revealed that patients with multiple myeloma (MM) had a lower likelihood of developing detectable antibodies after COVID-19 vaccination compared to healthy controls (Log odds ratio with 95% CI: -3.34 [-4.08, -2.60]). The analysis of antibody response after different doses showed consistent lower seropositivity in MM patients (after first dose: -2.09, [-3.49, -0.69], second: -3.80, 95%CI [-4.71, -3.01], a booster dose: -3.03, [-5.91, -0.15]). However, there was no significant difference in the mean level of anti-S antibodies between MM patients and controls (Cohen's d -0.72, [-1.86, 0.43]). Evaluation of T-cell responses indicated diminished T-cell-mediated immunity in MM patients compared to controls. Seven studies reported clinical response, with breakthrough infections observed in vaccinated MM patients. CONCLUSIONS: These findings highlight the impaired humoral and cellular immune responses in MM patients after COVID-19 vaccination, suggesting the need for further investigation and potential interventions.

Immune checkpoint inhibitors in advanced cutaneous melanoma: a systematic review and meta-analysis of efficacy and review of characteristics.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs. METHODS: We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). RESULTS: Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43-0.71; P<0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (P<0.001, R2 = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63-0.79, P<0.001 vs. HR = 0.63, 95%CI: 0.46-0.79, P<0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable. CONCLUSION: Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS (P < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma.

SARS-CoV-2 Infection and Severity in Patients with Hematologic Malignancies: A Systematic Review.

INTRODUCTION: Earlier reports described the possibility of higher SARS-CoV-2 infection and severity in patients with hematological malignancies. Given the importance and incidence of these malignancies, we aimed to systematically review SARS-CoV-2 infection and severity in patients with hematologic cancers. METHODS: We retrieved the relevant records by searching the keywords in online databases of PubMed, Web of Science, Cochrane, and Scopus on December 31st, 2021. A two-step screening; title/abstract and full-text screening, was employed to select the eligible studies. These eligible studies entered the final qualitative analysis. The study is adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of the results. RESULTS: Forty studies concerning different hematologic malignancies and the effect of COVID-19 infection on them were included in the final analysis. The findings showed that in general, the prevalence of SARS-CoV-2 infection and the severity of the disease are often higher in hematologic malignancies and the patients could experience higher morbidity and mortality compared to general populations. CONCLUSION: It appeared that individuals with hematologic malignancies are more vulnerable to COVID-19 infection and they experience more severe disease with higher mortality rates. The presence of other comorbidities could also deteriorate this situation. Further investigation is recommended to evaluate the outcome of COVID-19 infection in different subtypes of hematologic malignancies.

The burden of childhood and adolescent cancers in North Africa and the Middle East (NAME) region: findings from the Global Burden of Disease study 2019.

INTRODUCTION: Despite the significant burden of childhood and adolescent cancers, no specific studies recently discussed the burden of cancer in this group in the North Africa and the Middle East (NAME) region. Therefore, we aimed to study the burden of cancers in this group in this region. MATERIALS AND METHODS: We retrieved the Global Burden of Disease (GBD) data for children and adolescent cancers (0-19 years old) in the NAME region from 1990 to 2019. 21 types of neoplasms were grouped as "neoplasms", comprising 19 specific cancer groups as well as "other malignant neoplasms" and "other neoplasms". Three significant parameters of incidence, deaths, and Disability-Adjusted Life Years (DALYs) were studied. The data are presented with 95% uncertainty intervals (UI), and reported rates per 100,000. RESULTS: In 2019, almost 6 million (95% UI: 4.166 M-8.405 M) new cases and 11,560(9770-13,578) deaths due to neoplasms occurred in the NAME region. Incidence was higher in females (3.4 M), while deaths (6226 of overall 11,560) and DALYs (501,118 of overall 933,885) were estimated as higher in males. Incidence rates did not significantly change since 1990, while deaths and DALYs rates declined significantly. After excluding "other malignant neoplasms" and "other neoplasms", leukemia was responsible for the highest number of incidence and deaths (incidence: 10,629(8237-13,081), deaths: 4053(3135-5013), followed by brain and central nervous system cancers (incidence: 5897(4192-7134), deaths: 2446(1761-2960)), and non-Hodgkin lymphoma (incidence: 2741 (2237-3392), deaths: 790(645-962)). Incidence rates of neoplasms were similar for most countries, but countries varied more in terms of death rates. Afghanistan 8.9(6.5-11.9), Sudan 6.4(4.5-8.6), and the Syrian Arab Republic 5.6(4.3-8.3) had the highest overall death rates. CONCLUSION: The NAME region is observing relatively constant incidence rates and a decreasing pattern in the deaths and DALYs. Despite this success, several countries are lagging behind in development. Different issues such as economic problems, armed conflicts and political instabilities, lack of equipment or experienced staff or poor distribution, stigmatization and disbelief in the healthcare systems account for unfavorable numbers in some countries. Such problems require urgent solutions as new sophisticated and personalized cares raise the alarm for even more inequalities between high and low-income countries.

Severe hyponatremia in an infant with epidermolysis bullosa: a case report.

BACKGROUND: Epidermolysis bullosa is a rare inherited connective tissue disorder compromising cellular junctions. Blister formation is the first manifestation of epidermolysis bullosa. As cellular adhesion is affected, it can affect many organs. Due to compromised skin integrity, water loss and electrolyte imbalances are prevalent in these patients. However, hypernatremia is the usual observed sodium imbalance rather than hyponatremia. CASE PRESENTATION: The patient was a 48-day-old Iranian male infant born near term. He was diagnosed with epidermolysis bullosa at 1 month of age. The patient was brought to the pediatrics center with apnea and respiratory distress, and was intubated and admitted to the pediatric intensive care unit. His symptoms started 4 days before the admission with vomiting and poor feeding, and the patient later developed loss of consciousness. Vital signs revealed a pulse rate of 154 beats per minute, respiratory rate of 70 per minute, a temporal temperature of 36.5 °C, nondetectable blood pressure, and oxygen saturation of 96%. The patient was anuric at presentation and was rehydrated. Physical examination showed bolus eruptions all over the body but not in mucosal membranes. Important laboratory findings were white blood cell count of 41,000/mm3 with 68% neutrophils, hemoglobin of 10.8 g/dL, platelet count of 856,000/mm2, negative C-reactive protein (CRP), blood sugar of 514 mg/dL, urea of 129 mg/dL, sodium of 98 mg/dL, corrected sodium of 105 mg/dL, potassium of 5.5 mg/dL, serum creatinine of 1.7 mg/dL, and serum procalcitonin of more than 75 ng/mL. Urine analysis revealed many red blood cells. Brain computed tomography demonstrated loss of differentiation between gray and white matter and effacement of cortical sulci suggesting severe cytotoxic edema. We administered 3% hypertonic saline and corrected the plasma sodium levels, and provided the patient with multiple doses of mannitol as well as antibiotics due to the leukocytosis. Subsequently, after 3 days in pediatric intensive care unit, the symptoms of brain edema resolved, and after 4 days, he was weaned from the ventilator and extubated. Later he was discharged from the pediatric intensive care unit. CONCLUSION: This study illustrates the possibility of severe hyponatremia in patients with epidermolysis bullosa to clinicians. Although uncommon, knowledge on such possibilities is vital due to the possible detrimental outcomes for patients.

A global, regional, and national survey on burden and Quality of Care Index (QCI) of bladder cancer: The global burden of disease study 1990-2019.

INTRODUCTION: Bladder cancer (BCa) is the second most common genitourinary cancer and among the leading causes of cancer-related deaths. We aimed to assess BCa quality of care (QOC) utilizing a novel multi-variable quality of care index (QCI). MATERIALS AND METHODS: Data were retrieved from the Global Burden of Disease 1990-2019 database. QCI scores were calculated using four indices of prevalence-to-incidence ratio, Disability-Adjusted Life Years-to-prevalence ratio, mortality-to-incidence ratio, and Years of Life Lost-to-Years Lived with Disability ratio. We used principal component analysis to allocate 0-100 QCI scores based on region, age groups, year, and gender. RESULTS: Global burden of BCa is on the rise with 524,305 (95% UI 475,952-569,434) new BCa cases and 228,735 (95% UI 210743-243193) deaths in 2019, but age-standardized incidence and mortality rates did not increase. Global age-standardized QCI improved from 75.7% in 1990 to 80.9% in 2019. The European and African regions had the highest and lowest age-standardized QCI of 89.7% and 37.6%, respectively. Higher Socio-demographic index (SDI) quintiles had better QCI scores, ranging from 90.1% in high SDI to 30.2% in low SDI countries in 2019; however, 5-year QCI improvements from 2014 to 2019 were 0.0 for high and 4.7 for low SDI countries. CONCLUSION: The global QCI increased in the last 30 years, but the gender disparities remained relatively unchanged despite substantial improvements in several regions. Higher SDI quintiles had superior QOC and less gender- and age-based inequalities compared to lower SDI countries. We encourage countries to implement the learned lessons and improve their QOC shortcomings.

Feasibility, safety, and effectiveness of adult-sized instruments in pediatric percutaneous nephrolithotomy: A systematic review and meta-analysis.

INTRODUCTION: Little evidence exists regarding the benefits and disadvantages of adult-sized instruments for Percutaneous Nephrolithotomy (PCNL) in pediatric patients. This systematic review aims to clarify the safety and efficacy of this approach. MATERIALS AND METHODS: We conducted a systematic literature review using databases of PubMed, Scopus, Embase, Web of Science, and Cochrane and included studies that evaluated PCNL in children. All identified records underwent two-phase title/abstract and full-text screening. Pediatric patients were defined as 17 years or younger, and adult-sized instruments as 24Fr and above. The primary outcomes were success (stone-free) rate and surgical complications obtained from studies comparing adult-sized and pediatric-sized instruments. RESULTS: A total of 84 abstracts and 16 full text article were assessed till July 2021 and 6 studies were included. All studies were retrospective. Number of accesses (Odds ratio (OR), adult-sized to pediatric-sized: 0.96, 95% CI: 0.52-1.78, p = 0.89), initial stone-free rate (OR: 0.73, 95% CI: 0.42-1.27, p = 0.26), final stone-free rate (OR: 1.14, 95% CI: 0.38-3.44, p = 0.82), and residual stones (OR: 0.79, 95% CI: 0.42-1.49, p = 0.46) could be analyzed, none with significant differences. Overall complication rates did not differ significantly between the groups. However, one study reported more grade III/IV complications in the adult-sized instrument group. The adult-sized instrument group had a higher hemoglobin/hematocrit decrease in 3 studies. Duration of surgery, fluoroscopy time, length of hospital stay, times to nephrostomy tube removal, and transfusion rate could not be assessed in meta-analysis; however, they were comparable between the adult-sized and pediatric-sized groups. Studies also showed that adult-sized instruments are applicable in children younger than 3 years and those with staghorn calculi as well as in fluoroscopy-free ultrasound-guided PCNL. CONCLUSION: Adult-sized instruments had comparable outcomes to the pediatric-sized ones and can be applied in pediatric PCNL when factors such as accessibility justify their use. The number and design of the studies restrict the reliability of the comparisons. Therefore, future studies with improved methodology may better reveal the impact of instruments on the outcome of PCNL in children.

Vaccines for COVID-19: A Systematic Review of Feasibility and Effectiveness.

INTRODUCTION: Many potential vaccines for COVID-19 are being studied and developed. Several studies have reported on the safety and efficacy of these vaccines. This systematic review aimed to report on the current evidence concerning the feasibility and effectiveness of vaccines for COVID-19. METHODS: A systematic search was carried out utilizing the keywords in the online databases, including Scopus, Web of Science, PubMed, Embase, and Cochrane. We included both human and non-human studies because of the vaccine novelty, limiting our ability to include sufficient human studies. RESULTS: This review showed several SARS-CoV-2 vaccines to be currently under development using different platforms, including eight vaccines that are adenovirus-based vectors, six vaccines that are RNA-based formulations, one vaccine being DNA-based formulation, and other vaccines using other platforms, including lipid nanoparticles. Although the safety and efficacy profiles of these vaccines are still under debate, some countries have allowed for emergency use of some vaccines in at-risk populations, such as healthcare workers and the elderly. CONCLUSION: It is crucial to gather as much clinically relevant evidence as possible regarding the immunogenicity, efficacy, and safety profiles of available vaccines and adhere wisely to CDC protocols and guidelines for vaccine production.

Orthopedic management of myelomeningocele with a multidisciplinary approach: a systematic review of the literature.

BACKGROUND: Myelomeningocele (MMC) is the most common and severe form of spina bifida and imposes a significant burden on patients and the healthcare system. Recently, the multidisciplinary management of MMC has become popular. Herein, we aimed to review the orthopedic management, outcomes, and complications of the of patients with MMC eyeing a multidisciplinary approach. METHODS: We searched PubMed and EMBASE to find relevant studies published before August 2020. All studies that included clinical management of MMC patients and published earlier than 2000 were considered for review on the condition that they reported at least one orthopedic intervention and the rate of complications. We excluded review articles, case reports, case series, letters, commentaries, editorials, and conference abstracts. The primary and secondary goals of our review were to report the outcomes and complication rates of multidisciplinary management for MMC patients. RESULTS: Twenty-six studies included data for the management of 229,791 patients with MMC and were selected. Sixteen studies reported multidisciplinary management in addition to orthopedic management. From those, 11 (42.31%) included urologic management, 13 (50%) neurosurgical management, 11 (42.31%) neurologic management, and 5 (19.23%) gastrointestinal management. All studies included postnatal operations and related management. No randomized clinical trial was found in our search. CONCLUSION: Orthopedic approaches play a key role in MMC management by alleviating spinal deformities, particularly scoliosis, and hip, foot, and ankle complications. However, the most appropriate management, whether surgical or non-surgical, may vary for different patients, given disease severity and the age of patients.

Chimeric Antigen Receptor (CAR) T Cell Therapy for Metastatic Melanoma: Challenges and Road Ahead.

Metastatic melanoma is the most aggressive and difficult to treat type of skin cancer, with a survival rate of less than 10%. Metastatic melanoma has conventionally been considered very difficult to treat; however, recent progress in understanding the cellular and molecular mechanisms involved in the tumorigenesis, metastasis and immune escape have led to the introduction of new therapies. These include targeted molecular therapy and novel immune-based approaches such as immune checkpoint blockade (ICB), tumor-infiltrating lymphocytes (TILs), and genetically engineered T-lymphocytes such as chimeric antigen receptor (CAR) T cells. Among these, CAR T cell therapy has recently made promising strides towards the treatment of advanced hematological and solid cancers. Although CAR T cell therapy might offer new hope for melanoma patients, it is not without its shortcomings, which include off-target toxicity, and the emergence of resistance to therapy (e.g., due to antigen loss), leading to eventual relapse. The present review will not only describe the basic steps of melanoma metastasis, but also discuss how CAR T cells could treat metastatic melanoma. We will outline specific strategies including combination approaches that could be used to overcome some limitations of CAR T cell therapy for metastatic melanoma.

Can children of the Sputnik V vaccine recipients become symptomatic?

Sputnik V is one of the most promising vaccines, utilizing an Adenovirus vector to cause immunity against SARS-CoV-2. Concerns existed against Adenovirus infection with this vaccine, although seemed to be a rare event. In this study, we observed that 15/18 (83%) of the children of the Sputnik V recipients became symptomatic and developed transient fever and chills for 1-2 days starting after 2-5 days following the vaccination of their parents that can be related to an Adenovirus infection. To our knowledge, this is the first study reporting such symptoms in the children of Sputnik V recipients, and the results should be validated by larger studies.

Effects of Androgen Deprivation Therapy on COVID-19 in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Transmembrane serine protease 2 (TMPRSS2) facilitates SARS-CoV-2 cellular entry. Androgens regulate this protein and may increase the risk of COVID-19. Therefore, androgen deprivation therapy (ADT) may protect patients with prostate cancer from SARS-CoV-2 infection or decrease the severity of the disease. Therefore, we conducted a meta-analysis to study the effect of androgen deprivation therapy (ADT) on COVID-19 in patients with prostate cancer. METHODS: We systematically searched PubMed, Embase, Scopus, and Cochrane databases. All records underwent a two-step screening process to identify the eligible studies. The registered PROSPERO number of this study was CRD42021228398. We evaluated the effect of ADT on the risk of infection, hospitalization, ICU admission, and mortality. RESULTS: Six studies met inclusion criteria and were evaluated in this study. We performed meta-analysis on four eligible studies. The overall incidence of COVID-19 was 2.65% among patients with prostate cancer receiving ADT. COVID-19 mortality rate was about 22.7% in ADT (+) patients. ADT did not decrease the risk of any of the major outcomes; infection risk (OR= 0.63, 95% CI= 0.27- 1.48, P = 0.29), hospitalization rate (OR= 0.51, 95% CI= 0.10- 2.53, P = 0.41), ICU admission (OR= 1.11, 95% CI= 0.43- 2.90, P = 0.82), and mortality risk (OR= 1.21, 95% CI= 0.34- 4.32, P = 0.77). CONCLUSION: We did not observe a protective effect on the risk of infection, hospitalization, ICU admission, and mortality in patients receiving ADT; therefore, it should not be considered as a prophylactic or treatment for COVID-19. On the other hand, ADT did not increase the mortality and morbidity of COVID-19 and should be considered a safe treatment for patients with prostate cancer during the pandemic. Further studies are necessary to confirm our findings.

Adverse Events Following Administration of Anti-CTLA4 Antibody Ipilimumab.

Ipilimumab, a monoclonal anti-CTLA4 antibody, paved the path for promising treatments, particularly in advanced forms of numerous cancers like melanoma. By blockading CTLA-4, ipilimumab can abolish the higher binding affinity of B7 for CTLA-4, setting CD28 free to act unlimited. This blockade can result in an amplified antitumor immune response, and thereby, boosting more effective tumor regression. However, this blockage can lead to diminished self-tolerance and yielding autoimmune complications. The current review aims to describe adverse events (AEs) following the administration of ipilimumab in different cancers as every benefit comes at a cost. We will also discuss AEs in two different categories, melanoma and non-melanoma, owing to the possible shining promises in treating non-melanoma cancers. As the melanoma settings are more studied than other cancers, it might even help predict the patterns related to the other types of cancers. This similarity also might help physicians to predict adverse events and correctly manage them in non-melanoma cancers using the extensive findings reported in the more-studied melanoma settings. Recognizing the adverse events is vital since most of the adverse events could be reverted while carefully implementing guidelines. Finally, we will also describe the observed effectiveness of ipilimumab in non-melanoma cancers. This effectiveness reveals the importance of understanding the profile of adverse events in this group, even though some have not received FDA approval yet. Further clinical trials and careful systematic reviews may be required to decipher the hidden aspects of therapies with ipilimumab and its related AEs.

Adjuvant vs. salvage Radiation Therapy after Radical Prostatectomy: Role of Decipher® in the Era of Personalized Medicine.

Prostate Cancer (PCa) is the most prevalent cancer in men. Radical Prostatectomy (RP) as a primary definitive treatment may be followed by adjuvant or salvage radiotherapy. However, there are some uncertainties about receiving immediate adjuvant radiation after RP in men with adverse pathological features versus early salvage radiation therapy. Decipher is a novel genomic classifier and almost all studies have confirmed Decipher as a reliable predictor of metastasis, recurrence and mortality. With the aid of Decipher, clinicians are able to determine the need for adjuvant versus salvage radiotherapy. Decipher has the potential to reduce decisional conflicts in clinical recommendations, and is cost-effective. However, further investigations are required to prove Decipher's role in clinical outcome improvement in patients receiving Decipher-based course of treatment compared with those receiving usual care.