Epidemiology of substance and opium use among adult residents of Tehran; a comprehensive report from Tehran cohort study (TeCS).

BACKGROUND: The prevalence and burden of substance and opium use have increased worldwide over the past decades. In light of rapid population changes in Tehran, we aimed to evaluate the prevalence of opium and other substance use among adult residents in Tehran, Iran. METHOD: From March 2016 to March 2019, we utilized data from 8 296 participants in the Tehran Cohort Study recruitment phase (TeCS). We calculated the age-sex-weighted prevalence of substance use and the geographic distribution of substance use in Tehran. We also used logistic regression analysis to determine possible determinants of opium use. RESULT: We analyzed data from 8 259 eligible participants with complete substance use data and the average age of participants was 53.7 ± 12.75 years. The prevalence of substance use was 5.6% (95% confidence interval [CI]: 4.6- 7.1%). Substance use was more common in males than females (Prevalence: 10.5% [95% CI: 8.6- 12.6%] vs. 0.5% [95% CI: 0.2- 1.2%], respectively). The age-sex weighted prevalence of substance use was 5.4% (95% CI: 4.6-7.1%). Moreover, opium was the most frequently used substance by 95.8% of substance users. Additionally, we found that male gender (Odds ratio [OR]: 12.1, P < 0.001), alcohol intake (OR: 1.3, P = 0.016), and smoking (OR: 8.5, P < 0.001) were independently associated with opium use. CONCLUSIONS: We found that the prevalence of substance use in Tehran was 5.6%, and opium was the most frequently used substance. In addition, male gender, lower levels of education, alcohol, and tobacco consumption are the main risk factors for substance use in Tehran. Healthcare providers and policymakers can utilize our results to implement preventive strategies to minimize substance use in Tehran.

A systematic review of procedural modalities in the treatment of notalgia paresthetica.

BACKGROUND: Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP. AIMS: We sought to comprehensively evaluate the role of procedural treatments for NP. METHODS: We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included. RESULTS: Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases. CONCLUSION: Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.

Prevalence of insufficient physical activity among adult residents of Tehran: a cross-sectional report from Tehran Cohort Study (TeCS).

BACKGROUND: Insufficient physical activity (PA) is a major risk factor for non-communicable diseases (NCDs) and one of the leading causes of premature mortality worldwide. This study examined the prevalence and independent determinants of insufficient PA among adults resident of Tehran utilizing Tehran Cohort Study Data (TeCS). METHOD: We used the recruitment phase data from the TeCS with complete data on PA. PA was assessed through a Likert-scaled question and categorized into three groups. Utilizing data from the 2016 national census, the age- and sex-weighted prevalence of insufficient PA in Tehran was determined. The adjusted logistic regression model is used to neutralize influencing factors and determine the factors associated with insufficient PA. RESULT: The weighted prevalence of insufficient PA was 16.9% among the 8213 adult citizens of Tehran, with a greater prevalence among females (19.0% vs. 14.8% among males). Additionally, older age groups, unemployed, housewives, and illiterate educated participants displayed a much higher prevalence of insufficient PA (p < 0.001). Moreover, Tehran's central and southern districts had higher rates of insufficient PA. Concerning the adjusted regression model, older age (Odds ratio [OR]: 4.26, 95% confidence interval [95% CI]: 3.24-5.60, p < 0.001), a lower education level (p < 0.001), unemployment (OR: 1.80, 95% CI: 1.28-2.55, p = 0.001), being a housewife (OR: 1.44, 95% CI: 1.15-1.80, p = 0.002), higher body mass index (BMI) (OR for BMI > 30: 1.85, 95% CI: 1.56-2.18, p < 0.001), opium consumption (OR: 1.92, 95% CI: 1.46-2.52, p < 0.001), diabetes mellitus (OR: 1.25, 95% CI: 1.06-1.48, p = 0.008), hypertension (OR: 1.29, 95% CI: 1.11-1.50, p = 0.001), and coronary artery diseases (OR: 1.30, 95% CI: 1.05-1.61, p = 0.018), were significantly associated with insufficient PA. CONCLUSIONS: The identified associated factors serve as a valuable guide for policymakers in developing tailored intervention strategies to address the needs of high-risk populations, particularly among older adults and females.

Parental Exposure to Morphine Before Conception Decreases Morphine and Cocaine-Induced Locomotor Sensitization in Male Offspring.

Repeated exposure to abused drugs leads to reorganizing synaptic connections in the brain, playing a pivotal role in the relapse process. Additionally, recent research has highlighted the impact of parental drug exposure before gestation on subsequent generations. This study aimed to explore the influence of parental morphine exposure 10 days prior to pregnancy on drug-induced locomotor sensitization. Adult male and female Wistar rats were categorized into morphine-exposed and control groups. Ten days after their last treatment, they were mated, and their male offspring underwent morphine, methamphetamine, cocaine, and nicotine-induced locomotor sensitization tests. The results indicated increased locomotor activity in both groups after drug exposure, although the changes were attenuated in morphine and cocaine sensitization among the offspring of morphine-exposed parents (MEPs). Western blotting analysis revealed altered levels of D2 dopamine receptors (D2DRs) in the prefrontal cortex and nucleus accumbens of the offspring from MEPs. Remarkably, despite not having direct in utero drug exposure, these offspring exhibited molecular alterations affecting morphine and cocaine-induced sensitization. The diminished sensitization to morphine and cocaine suggested the development of a tolerance phenotype in these offspring. The changes in D2DR levels in the brain might play a role in these adaptations.

Efficacy and safety of lasers versus topical medications for acanthosis nigricans and pseudo-acanthosis nigricans treatment: a systematic review.

Acanthosis nigricans (AN) is a cutaneous disorder identified by well-defined pigmented plaques mostly detected on skin folds. Timely diagnosis and treatment of AN is essential as it could be an early manifestation of an underlying condition. The treatment of choice for AN has not been determined yet. Our study aimed to compare the efficacy and safety of various lasers with topical medications, including cream and peel. PubMed, Scopus, and Web of Science databases, as well as the Google Scholar search engine, were thoroughly searched until May 1st, 2023. Study selection was restricted to clinical trials published in English language comparing lasers with topical treatments. This study followed the PRISMA guidelines for systematic reviews and meta-analyses. Out of 1748 studies, Six clinical trials met our inclusion criteria, with 133 patients. We examined laser therapies, including fractional CO2 laser, 1550-nm erbium fiber laser, and long-pulsed alexandrite laser, while the topical treatments comprised glycolic acid (GA) peel, retinoic acid peel, trichloroacetic acid (TCA) peel, and tretinoin cream. In two studies, GA peel demonstrated favorable results compared to fractional CO2 laser. Besides, fractional CO2 laser exhibited efficacy, surpassing TCA peel in AN management. Additionally, a fractional 1550-nm erbium fiber laser displayed superiority over tretinoin cream in reducing average roughness. Similarly, a long-pulsed alexandrite laser demonstrated its effectiveness in axillary AN treatment compared to the combination of tretinoin and ammonium lactate. Overall, the findings revealed that laser therapy was associated with superior results. Moreover, topical treatments are safe and efficacious in AN management.

Efficacy and safety of radiofrequency in the treatment of hidradenitis suppurativa; a systematic review.

BACKGROUND AND AIMS: Hidradenitis suppurativa (HS) is an inflammatory skin disease affecting apocrine gland-bearing sites of the body. Radiofrequency (RF) is a minimally invasive method that acts by minimizing thermal damage to the dermis, resulting in collagen synthesis and scar improvement. We systematically reviewed the efficacy and safety of RF in treating HS. METHODS: A systematic search was performed up to November 18th, 2023, in PubMed/Medline, Ovid Embase, and Web of Science. Clinical studies with English full texts were included. The National Institute of Health (NIH) Quality Assessment Tool for clinical trials and Methodological quality and synthesis of case series and case reports by Murad et al. were utilized for critical appraisal. RESULTS: Out of 55 identified studies, 11 met our inclusion criteria with 167 subjects who underwent RF therapy alone or combined with an intense pulsed laser (IPL), known as LAight®. LAight® significantly improved clinical outcomes in mild-to-moderate HS patients based on the Dermatology Life Quality Index (DLQI), International Hidradenitis Suppurativa Score System (IHS4), Pain-Numerical Rating Scale (NRS), and Hidradenitis Suppurativa Clinical Response (HiSCR). Moreover, RF therapy alone significantly alleviated the clinical manifestations in patients with mild-to-moderate HS. Additionally, fractional microneedling RF significantly decreased HS-associated inflammatory markers. RF was found to be safe with limited adverse events. However, in moderate-to-severe HS, RF has failed to yield satisfactory results. CONCLUSION: RF is a safe energy-based method with promising outcomes, especially for long-term application in mild-to-moderate HS. In moderate-to-severe cases, RF should be combined with a systemic medication for further beneficial impacts.

The Endo-lift Laser (Intralesional 1470 nm Diode Laser) for Dermatological Aesthetic Conditions: A Systematic Review.

BACKGROUND: The prominence of minimally invasive aesthetic approaches has become increasingly pivotal. The endo-lift laser method is an intralesional 1470 nm diode laser connected to a fiber that serves both therapeutic and aesthetic properties. We sought to evaluate the efficacy and safety of the endo-lift laser method for dermatological aesthetic applications. METHODS: PubMed, Ovid-Embase, and Web of Science were systematically searched up to November 5th, 2023. A citation search was also performed. The National Institute of Health (NIH) Quality Assessment Tool was used to evaluate the quality of the studies. RESULTS: Out of 339 articles, twenty-three relevant studies were included in the current review. Applying the endo-lift laser method for rejuvenation, including face and neck lifting, enhancing skin laxity, and disappearing wrinkles, folds, and lines, demonstrated favorable efficacy and safety profile. Moreover, most studies have shown that the endo-lift laser method is promising in eliminating the adipose tissue in the jowl, abdomen, thighs, and arms. The endo-lift laser technique was also efficacious in nose remodeling and blepharoplastic procedures, including treating eyelid and eyebrow ptosis, eye bag, eyebrow position, and eyelid laxity. Patients who suffer from several diseases, such as hidradenitis suppurativa, progressive lipodystrophy, acne vulgaris, scars, and keloids, benefit from procedural treatment with the endo-lift laser technique. Across all studies, the adverse events were mild and self-limiting. Investigating the endo-lift laser method in all aesthetic and therapeutic indications resulted in high patient satisfaction rates. CONCLUSION: The endo-lift laser technique has therapeutic effects and is recommended for various dermatological aesthetic indications. Further clinical studies with control groups and larger sample sizes are needed to acquire more reliable evidence. LEVELS OF EVIDENCE III AND IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

The role of lateral habenula NMDA receptors in tramadol-induced conditioning.

The role of the lateral habenula (LHb) as a hub for receiving and relaying signals from the limbic system to serotonergic, dopaminergic, and norepinephrinergic regions in the brainstem makes this area a critical region in the control of reward and addiction. Behavioral evidence reveals the vital role of the LHb in negative symptoms during withdrawal. In this investigation, we study the role of the LHb N-Methyl D-Aspartate receptor (NMDAR) in the modulation of tramadol reward. Male adult Wistar rats were used in this study. The effect of intra-LHb micro-injection of NMDAR agonist (NMDA, 0.1, 0.5, 2 µg/rat) and antagonist (D-AP5, 0.1, 0.5, 1 µg/rat) was evaluated in conditioned place preference (CPP) paradigm. The obtained results showed that intra-LHb administration of NMDA induced place aversion dose-dependently, while blockade of NMDAR in the LHb using D-AP5 micro-injection led to an increased preference score in the CPP task. Co-administration of NMDA (0.5 µg/rat) with tramadol (4 mg/kg) reduced preference score, while co-administration of D-AP5 (0.5 µg/rat) with a non-effective dose of tramadol (1 mg/kg) potentiate the rewarding effect of tramadol. LHb receives inputs from the limbic system and projects to the monoaminergic nuclei in the brainstem. It has been declared that NMDAR is expressed in LHb, and as obtained data revealed, these receptors could modulate the rewarding effect of tramadol. Therefore, NMDA receptors in the LHb might be a new target for modulating tramadol abuse.

The prevalence of permanent pacemaker implantation after open-heart surgeries; eight years of experience in Tehran heart center.

BACKGROUND: We aimed to evaluate the prevalence of permanent pacemaker implantation (PPI) among open-heart surgery patients. METHODS: We reviewed data from 23 461 patients undergoing open-heart surgeries between 2009 and 2016 in our heart center in Iran. A total of 18 070 patients (77%) had coronary artery bypass grafting (CABG), 3 598 (15.3%) valvular surgeries, and 1 793 (7.6%) congenital repair procedures. Finally, 125 patients who received PPI following open-heart surgeries were enrolled in our study. We defined the demographic and clinical characteristics of all these patients. RESULTS: PPI was required in 125 (0.53%) patients with an average age of 58 ± 15.3 years. The average hospitalization time after surgery and waiting time for PPI were 19.7 ± 10.2 and 11.4 ± 6.5 days, respectively. Atrial fibrillation was the dominant pre-operative cardiac conduction abnormality (29.6%). Also, the primary indication for PPI was complete heart block in 72 patients (57.6%). Patients in the CABG group were significantly older (P = 0.002) and were more likely to be male (P = 0.030). The valvular group longer bypass and cross-clamp times and had more left atrial abnormalities. In addition, the congenital defect group was younger and had longer ICU stay times. CONCLUSIONS: Based on our study findings, PPI was required in 0.53% of patients following open-heart surgery due to damage to the cardiac conduction system. The current study paves the way for future investigations to identify possible predictors of PPI in patients undergoing open-heart surgeries.

Predictors of Five-Year Survival after EVAR: 10-Year Experience of Single-Center Cohort Study.

BACKGROUND: Endovascular abdominal aortic repair (EVAR) is the main therapeutic option for repairing abdominal aortic aneurysms (AAAs). We aimed to determine the long-term outcomes of patients who underwent EVAR at our center. METHODS: In this retrospective cohort study, patients who underwent EVAR for intact isolated AAA at Tehran Heart Center between 2007 and 2017 were included. Clinical outcomes and the frequency of mortality were analyzed for follow-up periods. We calculated the 5-year survival rate and its predictors for our patients using Kaplan-Meier estimation. RESULTS: We included the data of all patients (154 patients, mean age = 70.7 [± 8.0] years, 96.1% men) who successfully underwent EVAR at our center. The most common risk factors were coronary artery disease (70.1%), hypertension (68.2%), smoking (64.9%), and dyslipidemia (39.6%). There was no mortality during the procedure. The median follow-up was 65.5 months. An average decrease of 9.07 mm (95% confidence interval: 6.9-11.2) occurred in the size of the AAA. During follow-up, 12 patients developed some complications, 49 died, and 7 did not complete the follow-up. The 5-year survival rate was 75% (3.9%). The independent predictors for 5-year survival were age (hazard ratio [HR] = 1.06, P = 0.002) and anemia (HR = 1.91, P = 0.029). Despite not being statistically significant, dyslipidemia (HR = 0.573, P = 0.078) and long intensive care unit/cardiac care unit stays (HR = 1.08, P = 0.070) were borderline mortality predictors. CONCLUSIONS: This study depicted an acceptable survival rate for patients who underwent EVAR at our center. Age and anemia, 2 modifiable predictors of 5-year survival, can probably prolong the survival rate of patients, which requires evaluation later.

Epidemiology and prevalence of tobacco use in Tehran; a report from the recruitment phase of Tehran cohort study.

INTRODUCTION: Tobacco use is a major health concern worldwide, especially in low/middle-income countries. We aimed to assess the prevalence of cigarette smoking, waterpipe, and pipe use in Tehran, Iran. METHODS: We used data from 8272 participants of the Tehran Cohort Study recruitment phase. Tobacco use was defined as a positive answer to using cigarettes, waterpipes, or pipes. Participants who did not report tobacco use during the interview but had a previous smoking history were categorized as former users. Age- and sex-weighted prevalence rates were calculated based on the national census data, and characteristics of current and former tobacco users were analyzed. RESULTS: Age- and sex-weighted prevalence of current tobacco users, cigarette smokers, waterpipe, and pipe users in Tehran was 19.8%, 14.9%, 6.1%, and 0.5%, respectively. Current tobacco use was higher in younger individuals (35-45 years: 23.4% vs. ≥ 75 years: 10.4%, P < 0.001) and men compared to women (32.9% vs. 7.7% P < 0.001). The prevalence of tobacco use increased with more years of education (> 12 years: 19.3% vs. illiterate: 9.7%, P < 0.001), lower body mass index (< 20 kg/m2: 31.3% vs. ≥ 35 kg/m2: 13.8%, P < 0.001), higher physical activity (high: 23.0% vs. low: 16.4%, P < 0.001), opium (user: 66.6% vs. non-user: 16.5%, P < 0.001), and alcohol use (drinker: 57.5% vs. non-drinker: 15.4%, P < 0.001). Waterpipe users were younger (46.1 vs. 53.2 years) and had a narrower gender gap in prevalence than cigarette smokers (male/female ratio in waterpipe users: 2.39 vs. cigarette smokers: 5.47). Opium (OR = 5.557, P < 0.001) and alcohol consumption (OR = 4.737, P < 0.001) were strongly associated with tobacco use. Hypertension was negatively associated with tobacco use (OR = 0.774, P = 0.005). CONCLUSION: The concerning prevalence of tobacco use in Tehran and its large gender gap for cigarette and waterpipe use warrant tailored preventive policies.

Prevalence, awareness, treatment, and control of type 2 diabetes mellitus among the adult residents of tehran: Tehran Cohort Study.

BACKGROUND: The prevalence of type 2 diabetes mellitus has increased in the past decades. We investigated the prevalence of diabetes and its awareness, treatment, and control among adult residents of Tehran. METHODS: We used the recruitment phase data of the Tehran Cohort study, enrolling a random sample of adult residents of Tehran aged ≥35 years. Diabetes was defined as self-report, current use of glucose-lowering medications, and/or fasting plasma glucose (FPG) ≥126mg/dl. Impaired fasting glucose (IFG) was defined as an FPG of 100-125mg/dl. Awareness was defined as diabetes self-report, treatment as receiving glucose-lowering medications, and glycemic control as FPG <126mg/dl. The age- and sex-weighted estimates were calculated using the 2016 national census. Logistic regression models were used to determine the factors associated with diabetes awareness, treatment, and control. RESULTS: A total of 8151 participants were included. Age- and sex-weighted prevalence of diabetes mellitus and IFG were 16.7% (95% CI: 15.1-18.4) and 25.1% (95% CI: 23.1-27.1), respectively. Diabetes was more prevalent in the eastern and central districts of Tehran. Advanced age (OR per 1-year increase: 1.026, 95% CI: 1.021-1.030), male sex (OR: 1.716, 95% CI: 1.543-1.909), higher BMI levels (OR for BMI ≥35 vs. <20 kg/m2: 4.852, 95% CI: 3.365-6.998), pre-existing hypertension (OR: 1.552, 95% CI: 1.378-1.747), dyslipidemia (OR: 1.692, 95% CI: 1.521-1.883), and chronic kidney disease (OR: 1.650, 95% CI: 1.019-2.673) were associated with an increased odds of diabetes mellitus. On the contrary, diabetes mellitus was less likely in current tobacco (OR: 0.872, 95% CI: 0.765-0.994) and alcohol users (OR: 0.836, 95% CI: 0.703-0.994) compared to non-users. Among diabetic individuals, 82.8% were aware of their condition, 71.9% received treatment, and 31.7% of treated patients had adequate glycemic control. Advanced age and pre-existing comorbidities, including hypertension and dyslipidemia, were associated with higher diabetes awareness and treatment. Furthermore, advanced age, higher levels of education, and female sex were determinants of better glycemic control among treated diabetic participants. CONCLUSION: There is a high prevalence of diabetes and IFG among adult residents of Tehran. Additionally, more than two-thirds of treated diabetics living in Tehran remain uncontrolled.

Tumor necrosis factor inhibitors and janus kinase inhibitors in the treatment of cicatricial alopecia: A systematic review.

BACKGROUND: Cicatricial alopecia (CA) refers to various conditions that result in permanent hair loss. Treatment of CA has always been challenging. Regarding immune-mediated pathophysiology for many CA subtypes, the administration of Janus kinase (JAK) and tumor necrosis factor (TNF) inhibitors have potentiated the treatments of CA. METHODS: After a thorough systematic search in PubMed/Medline, Embase, Web of Science, Scopus, Google Scholar, ClinicalTrials.gov, and WHO ICTRP, a total of 3,532 relevant records were retrieved and screened. Accordingly, 56 studies met the eligibility criteria and entered the review. RESULTS: Among JAK inhibitors, oral tofacitinib was the most frequently reported and the most effective treatment in improving signs and symptoms of CA with minimal adverse effects (AEs). Baricitinib was another JAK inhibitor with sustained improvement while causing mild AEs. As a TNF inhibitor, adalimumab induced a rapid and stable improvement in signs and symptoms in most patients with rare, tolerable AEs. Thalidomide was the other frequently reported yet controversial TNF inhibitor, which caused a rapid and significant improvement in the condition. However, it may result in mild to severe AEs, particularly neuropathies. Infliximab is a TNF inhibitor with mostly favorable results, albeit in a few patients caused treatable dermatological AEs. Apremilast and certolizumab pegol caused an incomplete amelioration of signs and symptoms with no AEs. Lenalidomide is another TNF inhibitor that can induce temporary improvement in CA with probable AEs. It is noteworthy that utilizing adalimumab, infliximab, etanercept, golimumab, and an anonymous TNF inhibitor has induced paradoxical CA and other A.E.s in some patients. CONCLUSION: Recent studies have recommended JAK and TNF inhibitors, especially oral tofacitinib and adalimumab, as a new modality or adjuvant therapy to previous medications for primary CA. Nonetheless, monitoring AEs on a regular basis is suggested, and further extensive studies are required before definitive recommendations.

A systematic review of Janus kinase inhibitors and spleen tyrosine kinase inhibitors for Hidradenitis suppurativa treatment.

BACKGROUNDS AND AIMS: Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over the last few years, with the advancement of novel treatment approaches. The current systematic review aims to evaluate the safety and efficacy of Janus kinase (JAK) inhibitors and spleen tyrosine kinase (Syk) inhibitors in treating HS. METHOD: A thorough systematic search was performed on PubMed/Medline, Web of Science, and Ovid Embase databases up to September 23th, 2023. Clinical studies published in English were included. RESULTS: Our search yielded ten articles with a total of 165 patients treated with four types of JAK inhibitors (upadacitinib, povorcitinib, tofacitinib, and baricitinib) and one Syk inhibitor (fostamatinib). Upadacitinib, povorcitinib, and tofacitinib improved clinical outcomes, with a significant reduction in hidradenitis suppurativa clinical response (HiSCR) and abscess and inflammatory nodule count (AN count) during the treatment period. Also, these drugs are well tolerated in most HS patients with minimal adverse events (AEs). Moreover, baricitinib depicted an amelioration in signs and symptoms of HS in one case report. Also, fostamatinib exhibited favorable tolerability throughout a 12-week in moderate-to-severe HS patients. The remarkable clinical improvement, as assessed through HiSCR and hidradenitis suppurativa severity (IHS4), corresponded closely with serological indicators of inflammation following fostamatinib administration was achieved. CONCLUSION: JAK and Syk inhibitors are potentially efficacious in managing moderate-to-severe HS since the proinflammatory cytokines are mediated by JAK and Syk signaling pathways. However, further research with a more rigorous examination is mandatory to evaluate such medication's long-term safety and efficacy.

Golimumab and certolizumab pegol for the treatment of hidradenitis suppurativa: a literature review and future perspective.

Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains a therapeutic challenge. The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitors, adalimumab, infliximab, and etanercept, are well studied in this patient population, and in some cases, HS was unresponsive to them. In recent years, evidence has been growing regarding the application of other anti-TNFs, including certolizumab pegol (CPZ) and golimumab. We sought to evaluate the overall safety and efficacy of golimumab and CPZ in the management of HS. A comprehensive search was performed on the PubMed, Scopus, Web of Science, and Ovid Embase databases, as well as the Google Scholar search engine from initiation to 31 August 2023. A total of nine and four studies used CPZ and golimumab to treat HS, respectively. Individuals with concomitant inflammatory immune-mediated diseases, pregnant females, and patients who were refractory to previous treatments achieved a Hidradenitis Suppurativa Clinical Response following CPZ administration. Also, golimumab showed promise in treating recalcitrant HS after the failure of other treatments, such as adalimumab and anti-interleukin-1. CPZ and golimumab can be efficacious treatment options for moderate-to-severe HS, especially in patients who are unresponsive to other TNF inhibitors, such as adalimumab.

The role of BAFF and BAFF-R inhibitors in the treatment of immune thrombocytopenia; a focused review.

Immune thrombocytopenia (ITP) is an autoimmune-driven disease characterized by increased destruction and impaired platelet production resulting in an enhanced risk of bleeding. Immunosuppressant agents are the most common treatment strategies for ITP. Despite their efficacy, these medications often cause unpredictable side effects. Recent investigations revealed that patients with ITP exhibit elevated B-cell activating factor (BAFF) levels in both their spleens and serum. Belimumab, a BAFF inhibitor, illustrated a promising therapeutic avenue for managing ITP by interfering with BAFF activity and long-lived plasma cell production. Both clinical and experimental studies have yielded positive outcomes when combining rituximab with an anti-BAFF monoclonal antibody in treating ITP. In addition, ianalumab, a monoclonal antibody with a dual mechanism that targets BAFF-R and deletes peripheral BAFF-R+ B cells, is currently being used for ITP treatment [NCT05885555]. The upcoming results from novel BAFF inhibitors, such as ianalumab, could offer clinicians an additional therapeutic option for treating ITP.

Preconception ethanol exposure changes anxiety, depressive and checking-like behavior and alter the expression levels of MAO-B in male offspring.

Alcohol use, which alters the epigenome, increases the probability that it could affect subsequent generations, even if they were never directly exposed to ethanol or even in utero. We explored the effects of parental ethanol exposure before conception on behavioral changes in the offspring. Considering the role of Monoamine oxidase-B (MAO-B) in dopamine turnover in the prefrontal cortex (PFC) and its influence on behavior, and taking into account that ethanol exposure could alter MAO-B, we assessed the protein levels in the offspring. Male and female rats were exposed to ethanol for 30 days and then allowed ten days of abstinence. Afterward, they were mated with either control or ethanol-exposed rats. The F1 and F2 male offspring underwent tests to assess behavioral changes. Additionally, the levels of MAO-B in the PFC were evaluated. Results revealed that in the F1, anxiety increased only in the bi-parental ethanol-exposed male offspring in the elevated plus maze test (p < 0.05), while depressive-like behavior rose only in maternal and bi-parental ethanol-exposed offspring (p < 0.01). However, compulsive-like behavior increased in all ethanol-exposed offspring (p < 0.01). No significant phenotypic changes were observed in the F2. The levels of MAO-B in the PFC increased in the maternal (p < 0.05) and bi-parental ethanol-exposed offspring (p < 0.01). Our study demonstrates that parental ethanol exposure, even in the days preceding mating, adversely affects behaviors and induces molecular changes in the brain. Given these findings, it becomes imperative to monitor children exposed to parental (especially maternal) ethanol for the prevention of mental disorders.