Revisiting Recent Tissue Engineering Technologies in Alveolar Cleft Reconstruction.

Tissue engineering and regenerative medicine have received significant attention in treating degenerative disorders and presented unique opportunities for researchers. The latest research on tissue engineering and regenerative medicine to reconstruct the alveolar cleft has been reviewed in this study. Three approaches have been used to reconstruct alveolar cleft: Studies that used only stem cells or biomaterials and studies that reconstructed alveolar defects by tissue engineering using a combination of stem cells and biomaterials. Stem cells, biomaterials, and tissue-engineered constructs have shown promising results in the reconstruction of alveolar defects. However, some contrary issues, including stem cell durability and scaffold stability, were also observed. It seems that more prospective and comprehensive studies should be conducted to fully clarify the exact dimensions of the stem cells and tissue engineering reconstruction method in the therapy of alveolar cleft.

Three doses of a recombinant conjugated SARS-CoV-2 vaccine early after allogeneic hematopoietic stem cell transplantation: predicting indicators of a high serologic response-a prospective, single-arm study.

Background: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-binding domain (RBD)-tetanus toxoid (TT)-conjugated platform shortly after allo-HSCT in the developing country of Iran. Methods: This prospective, single-arm study aimed to investigate immunogenicity and its predictors following a three-dose SARS-CoV-2 RBD-TT-conjugated vaccine regimen administered at 4-week (± 1-week) intervals in patients within 3-12 months post allo-HSCT. An immune status ratio (ISR) was measured at baseline and 4 weeks (± 1 week) after each vaccine dose using a semiquantitative immunoassay. Using the median ISR as a cut-off point for immune response intensity, we performed a logistic regression analysis to determine the predictive impact of several baseline factors on the intensity of the serologic response following the third vaccination dose. Results: Thirty-six allo-HSCT recipients, with a mean age of 42.42 years and a median time of 133 days between hematopoietic stem cell transplant (allo-HSCT) and the start of vaccination, were analyzed. Our findings, using the generalized estimating equation (GEE) model, indicated that, compared with the baseline ISR of 1.55 [95% confidence interval (CI) 0.94 to 2.17], the ISR increased significantly during the three-dose SARS-CoV-2 vaccination regimen. The ISR reached 2.32 (95% CI 1.84 to 2.79; p = 0.010) after the second dose and 3.87 (95% CI 3.25 to 4.48; p = 0.001) after the third dose of vaccine, reflecting 69.44% and 91.66% seropositivity, respectively. In a multivariate logistic regression analysis, the female sex of the donor [odds ratio (OR) 8.67; p = 0.028] and a higher level donor ISR at allo-HSCT (OR 3.56; p = 0.050) were the two positive predictors of strong immune response following the third vaccine dose. No serious adverse events (i.e., grades 3 and 4) were observed following the vaccination regimen. Conclusions: We concluded that early vaccination of allo-HSCT recipients with a three-dose RBD-TT-conjugated SARS-CoV-2 vaccine is safe and could improve the early post-allo-HSCT immune response. We further believe that the pre-allo-HSCT SARS-CoV-2 immunization of donors may enhance post-allo-HSCT seroconversion in allo-HSCT recipients who receive the entire course of the SARS-CoV-2 vaccine during the first year after allo-HSCT.

Comparable Outcomes of Pre- Versus Post-Tyrosine Kinase Inhibitor Era Treatment in Chronic Myeloid Leukemia: A Retrospective Cohort Study With Long-term Follow-up.

Imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was introduced after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia (CML). However, the long-term effects of allo-HSCT in chronic phase CML patients are mostly unknown. We retrospectively analyzed the outcomes of 204 patients with sibling donors who received peripheral stem cells and underwent allo-HSCT of chronic phase I (CP1) in the pre- and post-TKI era at Shariati Hospital in Tehran, Iran, from 1998 to 2017 and followed up till the end of 2021. The median follow-up time for all patients was 8.7 (SD = 0.54) years. Fifteen-year overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM) incidence were 65.70%, 57.83%, 17.56%, 13.17%, and 28.98%, respectively. Using multivariable analyses, the only risk factor increasing the hazard of death was the time between diagnosis to allo-HSCT greater than 1 year compared to this time less than 1 year by 74% [hazard ratio (HR) = 1.74, P = 0.039]. Also, age is a significant risk factor for DFS (HR = 1.03, P = 0.031). Our findings suggested that allo-HSCT is still an important treatment option for CP1 patients, especially those resistant to TKI treatment. TKI consumption can have a desirable effect on NRM after allo-HSCT for CP1 CML.

Retrospective Evaluation of Hairy Cell Leukemia Patients: Analysis of a Long-Term Single Center Data.

Background: Hairy cell leukemia (HCL) is a distinct lymphoproliferative disorder with unique circulating lymphocyte morphology. It is now regarded as an indolent disease yet treatable with purine analogs. We are going to present a complete long-term clinical and prognostic report of our HCL patients as a large cohort in Iran. Materials and Methods: All patients diagnosed with HCL, according to the World Health Organization (WHO) criteria, were enrolled in this study. They were referred to our academic center between 1995 and 2020. Treatment with a daily cladribine regimen was initiated as indicated and patients were followed. Survival data and clinical outcomes of patients were calculated. Results: A total of 50 patients were studied (76% male). The median time to treatment was 4.8 months and complete remission was achieved in 92% of patients. Nine patients (18%) experienced relapse with a median time to relapse of 47 months. After a median follow-up of 51 months, the median OS was not reached and after 234 months, the overall survival rate was 86%. Survival was worse in patients with non-classic HCL (vHCL) compared to classic HCL. Conclusion: Our long-term follow-up data confirmed the favorable outcomes of Iranian HCL patients with cladribine and provide a useful viewpoint of the disease.

The Impact of COVID-19 on Cancer Care in the Post Pandemic World: Five Major Lessons Learnt from Challenges and Countermeasures of Major Asian Cancer Centres.

OBJECTIVE: The COVID-19 pandemic has dramatically affected healthcare services around Asia. The Asian National Cancer Centres Alliance and the Asia-Pacific Organisation for Cancer Prevention collaborated to assess the mid- and long- term impact of COVID-19 to cancer care in Asia. METHODS: The two entities organised a combined symposium and post-meeting interactions among representatives of major cancer centres from seventeen Asian countries to outlining major challenges and countermeasures. RESULTS: Participating stakeholders distilled five big questions. 1) "Will there be an explosion of late-stage cancers after the pandemic?" To address and recover from perceived delayed prevention, screening, treatment and care challenges, collaboration of key stakeholders in the region and alignment in cancer care management, policy intervention and cancer registry initiatives would be of essential value. 2) "Operations and Finance" The pandemic has resulted in significant material and financial casualties. Flagged acute challenges (shortages of supplies, imposition of lockdown) as well as longer-standing reduction of financial revenue, manpower, international collaboration, and training should also be addressed. 3) "Will telemedicine and technological innovations revolutionize cancer care?" Deploying and implementing telemedicine such as teleconsultation and virtual tumour boards were considered invaluable. These innovations could become a new regular practice, leading to expansion of tele-collaboration through collaboration of institutions in the region. 4) "Will virtual conferences continue after the pandemic?" Virtual conferences during the pandemic have opened new doors for knowledge sharing, especially for representatives of low- and middle-income countries in the region, while saving time and costs of travel. 5) "How do we prepare for the next pandemic or international emergency?" Roadmaps for action to improve access to appropriate patient care and research were identified and scrutinised. CONCLUSION: Through addressing these five big questions, focused collaboration among members and with international organisations such as City Cancer Challenge will allow enhanced preparedness for future international emergencies.
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Solitary Rectal Ulcer Syndrome: A Narrative Review.

Solitary rectal ulcer syndrome is a multifactorial pathology, which entails a variety of clinical, histologic and endoscopic aspects that needs step-wise logical approach for management especially in relapsing refractory cases. Apart from the diagnostic dilemma that may be faced due to similarities of presentation with inflammatory bowel diseases or colorectal neoplastic lesions, the syndrome also overlaps with dyssynergic defecation syndrome, health anxiety disorder, obsessive compulsive disorder, and latent mucosal rectal prolapse, a systematic composite treatment modality including psychological, pharmacological, physiological and possibly surgical interventions are sometimes essential. Selecting appropriate treatment in this condition not only affects clinical outcome but also patients' experience and further stigma of SRUS life-long. In this review, we will discuss the detailed pathophysiology, diagnostic and therapeutic approaches in dealing with solitary rectal ulcer syndrome.

Post-infectious Irritable Bowel Syndrome: A Narrative Review.

The Irritable bowel syndrome (IBS) is a functional disorder of alimentary system, which may be caused by infectious gastroenteritis determined as post infectious irritable bowel syndrome (PI-IBS). The prevalence of PI-IBS is reported to be 4-36% in patients with infectious gastroenteritis. The exact mechanism leading to PI-IBS is not fully understood and some factors pertaining to infectious agent and host response may have a role. Rome IV diagnostic criteria provided new definition for PI-IBS. Though it is now considered a well-defined functional disorder of gastrointestinal system, no specific treatment is yet available for PI-IBS. This article reviews the latest issues on these heading about PI-IBS.

The Correlation Between Liver Fat Content and Ulcerative Colitis Disease Severity.

To evaluate the association between disease severity and hepatic steatosis in patients with ulcerative colitis (UC) and non-alcoholic steatohepatitis (NASH). Consecutively selected UC patients admitted to the gastroenterology clinic were enrolled in the study. UC severity was assessed by Truelove and Witts classification. Patients with severe UC were excluded from the study. NASH was determined based on persistently elevated serum aminotransferase levels and detection of fatty liver ultrasound. Patients with other etiologies for elevated aminotransferase levels were excluded. Liver fat content (LFC) was assessed by measuring liver fat score (LFS). One hundred patients (42% male) were included in the study. According to liver ultrasound examination, 62 (%) patients were identified with grade 1 fatty liver disease, and 38 (%) patients were classified as advanced (grade 2 and 3) fatty liver disease. Sixty-one patients had left-sided UC and (46%) had mild UC disease severity index. LFS was significantly higher in UC patients with the moderate disease than patients with mild disease (3.53±2.68 vs. 5.89±2.85, respectively; P<0.01). Nevertheless, no significant difference was observed in LFS regarding UC extension. There was no significant difference between NASH ultrasound grades in view of UC severity and extension. LFC might be associated with UC severity.

Medical Journal Club as a New Method of Education: Modifications for Improvement.

BACKGROUND: The emerging goals of journal clubs are now considered to be teaching critical appraisal skills and how to use evidence based medicine in practice. Although journal clubs are well accredited, designing the right format to keep members stimulated and educated remains a great challenge. METHODS: We conducted journal club structure modifications in internal medicine residency program of a university affiliated hospital. Initially, group-based sessions identified feasible changes and baseline data concerning residents` knowledge of evidence based medicine (EBM) was collected using a questionnaire. Modifications were implemented and a second set of group discussions and data collection took place after 12 months. RESULTS: A total of 78 (86.7%) internal medicine residents participated. The most important identified changes were schedule adjustments and setting new goals regarding EBM, medical statistics and critical appraisal teaching. Group discussion showed increased satisfaction and questionnaire assessments showed significant improvement in residents' knowledge of EBM. CONCLUSIONS: Redesigning journal clubs with emphasis on regularity and setting new horizons basically improves their effectiveness. Assigning entire sessions to augment participants` skills in new areas of knowledge is a unique way to fit journal clubs as a novel and innovative teaching practice.

Diagnostic yield of EUS-guided FNA for malignant biliary stricture: a systematic review and meta-analysis.

BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is increasingly being used for tissue diagnosis of extrahepatic biliary strictures. The aim of this study was to determine the diagnostic yield of EUS-FNA in malignant biliary strictures. METHODS: A comprehensive literature review was carried out by 2 reviewers for studies evaluating the accuracy of EUS-FNA in biliary stricture. A meta-analysis was performed to determine the pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio for EUS-FNA of extrahepatic biliary stricture. A Quality Assessment of Diagnostic Accuracy Studies questionnaire was used to assess the quality of the selected studies. Several sensitivity analyses were performed to assess the effect of the quality of the studies on the accuracy of the final results of the meta-analysis. RESULTS: Twenty studies involving 957 patients met inclusion criteria and were included in the meta-analysis. The pooled sensitivity and specificity of EUS-FNA for diagnosis of malignant biliary stricture were 80% (95% confidence interval [CI], 74%-86%), and 97% (95% CI, 94%-99%), respectively. The pooled positive likelihood ratio was 12.35 (95% CI, 7.37-20.72), and the negative likelihood ratio was 0.26 (95% CI, 0.18-0.38). The pooled diagnostic odds ratio for diagnosing a malignant biliary stricture was 70.53 (95% CI, 38.62-128.82). The area under the receiver-operating characteristic curve was 0.97. Sensitivity analyses showed that the quality of the included studies did not affect the accuracy of the final results of the meta-analysis. CONCLUSION: This meta-analysis demonstrates that EUS-FNA is sensitive and highly specific for diagnosing malignancy in biliary strictures. Further studies are needed to compare EUS--FNA with emerging methods including cholangioscopy-guided biopsy and laser endomicroscopy.

The Comparison of WHOQOL-BREF with Disease Specific Heath Related Quality of Life Questionnaire in Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS) is one of the most common gastrointestinal disorders particularly affecting the quality of life (QOL). Evaluating QOL in IBS patients is a valuable method of defining a psychobiological pattern of disease. Various disease specific and general instruments are now available to measure health-related QOL (HRQOL) in IBS patients. Though, no comparison has been made between these tools especially in non-western countries. We aimed to compare QOL measures between two specific and general QOL questionnaires in a sample of Iranian IBS patients. A total of 250 IBS patients were diagnosed based on Rome III criteria (mean age 29.6 ± 9.6 years). HRQOL was assessed using disease specific quality of life for IBS (IBS-QOL) and generic World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaires. Patients also completed Speilberger`s "State/Trait Anxiety Inventory" and "Beck Depression Inventory-II" for the evaluation of anxiety and depression symptoms. The severity of symptoms was independently associated with HRQOL in patients using WHOQOL-BREF and IBS-QOL (r = -0.48 and -0.39 respectively, P < 0.001). In linear regression analysis, a strong correlation was observed between the HRQOL scores of IBS-QOL and the WHOQOL-BREF questionnaires (standard ß = 0.86 (95%CI: 1.15 - 1.44), P value < 0.001). Controlling for anxiety and depression symptoms did not influence the strength of observed correlation. The WHOQOL-BREF is a psychometrically sound, rapid and convenient instrument whose HRQOL measure is as valid and accurate as the disease-specific IBS-QOL questionnaire. It seems reasonable to use the WHOQOL-BREF alongside the IBS-QOL.

Analysis of switched memory B cells in patients with IgA deficiency.

BACKGROUND: Selective IgA deficiency (SIGAD) is the most common primary antibody deficiency, characterized by significant decreased serum levels of IgA in the presence of normal IgG and IgM. Despite several investigations into the nature of the disease, the exact pathophysiology of SIGAD is still unknown. METHODS: In this study, switched memory B cells (CD19+/CD27+/IgD- cell population) of 28 patients with SIGAD and 28 matched healthy controls were investigated using flow cytometry. RESULTS: The percentage of switched memory B cells in all healthy controls was more than 0.4%. In SIGAD patients, who were classified as group I, the percentage of switched memory B cells was less than 0.4% (0.34 ± 0.06) in 7 patients (25%). The remaining 21 patients were designated as group II (1.74 ± 0.12%). The mean concentration of IgG in group I was significantly lower than in group II (1,014 ± 278 vs. 1,388 ± 406 mg/dl, p = 0.028). Comparison of clinical features between the 2 groups revealed that episodes of pneumonia during the course of disease were significantly higher in group I than in group II (p = 0.002). Autoimmune diseases in group I (57.1%) were also significantly higher (p = 0.01) than in group II (23.8%). The prevalence of bronchiectasis was 57% in group I, while only 1 patient (4.7%) in group II developed bronchiectasis (p = 0.006). Specific antibody deficiency in group I was documented in 5 patients and in group II in 4 patients (p = 0.01). CONCLUSIONS: The classification of SIGAD patients by assessment of switched memory B cells could help physicians with the clinical prognosis for these patients, whereas the patients with reduced switched memory B cells are prone to severe phenotypes.

Effect of anti-epileptic drugs on serum immunoglobulin levels in children.

Epilepsy is one of the most frequent neurological disorders. Despite the advances and improvements in treatment of seizure disorders, immunologic alterations related to anticonvulsant drugs have been described. The aim of this paper is to assess the effect of some antiepileptic drugs on serum immunoglobulin levels in epileptic patients. Seventy-one patients with epilepsy were included in the study. Participants were divided into three groups based on their treatment with carbamazepine (n=33), sodium valproate (n=22) or phenobarbital (n=16) as monotherapy. Three samples were taken from each patient and serum immunoglobulin levels were measured before treatment, 3 months and 6 months after therapy. Overall, eleven patients out of 71 (15.5%) had a decrease in at least one serum immunoglobulin level (more than 2SD below age-matched control). In the patients receiving carbamazepine, 8 patients (24.2%) showed significant decline in at least one immunoglobulin (3 cases in IgA and 5 cases in IgG). In the group of treated with sodium valproate, 2 patients showed significant decrease in serum IgA level. Results of the last group indicated a significant reduction in serum IgG concentration only in one patient. No patient at all showed significant decrease in serum IgM level. This study suggests that anti-epileptic drugs could reduce serum immunoglobulins, especially IgA and IgG; among them carbamazepine effect is of more concern.

Effect of anti-epileptic drugs on serum level of IgG subclasses.

OBJECTIVE: There are some controversial studies on effects of anti-epileptic drugs (AEDs) on serum IgG subclasses; however, the role of these medications is still unclear. The aim of this study was evaluation the effects of anti-epileptic drugs on serum concentration of IgG and its subclasses METHODS: Serum IgG and IgG subclasses of 61 newly diagnosed epileptic patients were measured at the beginning of monotherapy with carbamazepine, sodium valproate, and phenobarbital, and 6 months later. Measurement of IgG and its subclasses was performed using nephlometry and ELISA techniques, respectively. FINDINGS: Reduction of at least one IgG subclass was found in 6 patients 6 months after treatment with AEDs. Among 27 patients receiving carbamazepine, decrease in at least one serum IgG subclass level was found in 5 patients. Among 20 patients using sodium valproate, only one patient showed decrease in IgG2 subclass. None of the 14 patients using phenobarbital revealed significant decrease in IgG subclasses. No infection was seen in the patients with reduction of subclasses. CONCLUSION: Although in our study, children with selective IgG subclass deficiency were asymptomatic, assessment of serum immunoglobulin levels could be recommended at starting the administration of AEDs and in serial intervals afterward in epileptic patients.