Can the bone marrow harvest volume be reduced safely in hematopoietic stem cell transplantation with pediatric sibling donors?

Background@#Reduced harvest volumes in pediatric donors appear to have the potential to reduce donor-associated risks while maintaining engraftment in recipients; however, the allowable harvest volume reduction remains undefined. @*Methods@#We retrospectively analyzed the data pairs of 553 bone marrow (BM) harvests from pediatric (age at harvest ＜18 yr) sibling donors and clinical outcomes of 553 pediatric (age at infusion ＜14 yr) transplant-naïve recipients to assess the optimal BM harvest volume needed from pediatric donors to obtain the desired CD34+ cell count (≥3.0×10 6 cells per kg of recipient weight), and to study its impact on the clinical outcomes of transplantation in pediatric recipients. @*Results@#The minimum desired CD34+ cell count of ≥3.0×10 6 per kg of recipient weight was achieved for 506 (95.3%) of donor-recipient pairs. The median CD34+ cell yield was 6.4×10 6 per kg of recipient weight (range, 1.2‒33.8×10 6 ) in donors younger than 5 years old at harvest, 4.7×10 6 (range, 0.3‒28.5×10 6 ) in donors aged 5‒10 years and 2.1×10 6 range, 0.3‒11.3×10 6 ) in donors older than 10 years (P ＜0.001). @*Conclusion@#The infused CD34+ cell dose (×10 6 cells/kg of recipient weight) had no impact on GRFS; however, a CD34+ cell dose of ＞7×10 6 cells/kg of recipient weight did not improve hematopoietic recovery

Endodontic file separation and its management among dentists in Punjab, Pakistan: a cross-sectional study

The study aimed to find the incidence and awareness of endodontic instrument separation and its management among dental house officers, postgraduate trainees, demonstrators, consultants, and general dentists. Methods: This online questionnaire-based cross-sectional study was conducted with the approval of the IRB in private and public dental hospitals and dental clinics in Punjab. The authors developed the survey tool, which comprises 24 closed-ended items regarding demographics, the incidence of file separation, and awareness about its management. The data were analyzed using IBM SPSS version 24. The Chi-Square Test was used to compare percentages of categorical variables. Results: Postgraduate trainees experienced the most instrument separations (43.6%), made the most retrieval attempts (49.2%), and experienced the most secondary errors during retrieval (52.1%) (p<0.001). Around four out of ten respondents always informed the patients (39.6%) and department (41.6%) about errors. Manual files (69.8%), stainless steel files (75.8%), and short files (60.4%) were more frequently separated, and the most frequent cause was older fatigue files (57.7%). Manual files were more frequently broken in public dental institutes (p=0.003). Two-thirds of the file separations (72.5%) occurred during cleaning and shaping in the apical third of molars (65.1%), especially in mesiolingual canal (56.4%). Bypass attempt was the most common in symptomatic teeth (47.7%). Conclusions: Preventive approaches such as limiting file reuse and constructing a glide path can reduce the occurrence of file separation. Operators should be familiar with the number of uses of the instrument before fatigue and should be trained through workshops and refresher courses

Mucosal Schwann cell hamartoma of the gallbladder

Mucosal Schwann cell hamartoma (MSCH) is a rare benign neurogenic tumor characterized by pure S100p positive spindle cell proliferation. Most cases occur in the distal colon. Involvement of the gall bladder is exceedingly rare. There have been no reports of recurrence or a syndromic association with MSCH. Herein, we describe a case of MSCH of the gallbladder in a 55-year-old female patient with prior history of gastrointestinal neurofibromas who presented with abdominal pain. MR imaging revealed choledocholithiasis, gallbladder thickening, and marked biliary and pancreatic ductal dilation. The patient subsequently underwent cholecystectomy with choledochoduodenostomy. Histologic evaluation of the gallbladder showed diffuse expansion of the mucosa with S100p positive cells with spindly nuclei and indistinct cytoplasmic borders and diagnosis of MSCH of the gallbladder was rendered.

Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis

Background@#Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients. @*Methods@#FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed. @*Results@#Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P =0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P =0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P =0.001). @*Conclusion@#Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant.

Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis

Background@#Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients. @*Methods@#FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed. @*Results@#Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P =0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P =0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P =0.001). @*Conclusion@#Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant.

Metastasis from tongue squamous cell carcinoma to the kidney

Metastasis to the kidney from other primary sites is extremely rare. Previous studies reported the lung as the most common primary site. Distant metastasis from the tongue to the kidney is exceedingly rare. Herein, we describe a case of metastatic squamous cell carcinoma to the kidney in a 71-year-old male with a detailed discussion of differentiating it from potential mimickers. The patient underwent a total glossectomy and bilateral cervical lymph node dissection. A diagnosis of well-differentiated squamous cell carcinoma of the tongue was rendered and the tumor was staged pT3 pN3b. Within two years of initial presentation, the patient developed widely metastatic disease, including pulmonary nodules, renal masses, left adrenal mass, and pancreatic mass. Accurate diagnosis of a secondary involvement of the kidney by a metastatic tumor requires the appropriate correlation of clinical and imaging findings as well as morphologic and immunohistochemical clues.

Omega 3 Fatty Acids and COVID-19:A Comprehensive Review

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to “cytokine storm”. This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.

Omega 3 Fatty Acids and COVID-19:A Comprehensive Review

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to “cytokine storm”. This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.

Medical student syndrome; the affliction in medical students

Objective: The aim of the study is to find out the prevalence of Medical Student Syndrome [MSS] in Pakistan and its association with age, maturity level and the degree of medical knowledge. Study Design: Descriptive cross-sectional study. Place and Duration of Study: The survey was completed in one year, from Jul 2016 to Jul 2017

Material and Methods: A self-designed, self-explanatory questionnaire was used. The link of the questionnaire was disseminated electronically. The data were analyzed by using Statistical Package for Social Sciences [SPSS-22]

Results: Total 129 responses were received from the students of different medical colleges/universities of Pakistan. Mean age of the participants was 21.94 years. Among the respondents 43% were males while 57% were females. Maximum participants were from final year. Majority of the respondents that is about 81% reported they had symptoms of the diseases they study, yet 44% pursued and moved forward. Among them 28% of the respondents said that they investigated their felt symptoms further, of which maximum were from 3rd year. Only 43% of the students knew about the Medical Student Syndrome. Some of the respondents, about 22.8% admitted the fact that they used psychiatric medicines either for relaxing or sleep

Conclusion: It can be concluded that medical students are more vulnerable to conditions like Medical student syndrome so there is a need to counsel medical students about the symptoms of MSS as well as to support the students by discussing different techniques to subsist the stress level

Piperine attenuates the cancerous activity response in Neuro-2a cell line

Interactions of cancer cells with their microenvironment play a significant role in defining the severity of the disease. In search of novel compounds with anti-inflammatory and anticancerous capabilities, the effects of purified compound piperine were investigated in Neuro-2a cell line. The neuronal lineage of Neuro-2a cell line was confirmed by using antibody against Beta-III tubulin protein. The cells were treated with different concentrations of piperine [MuM: 10, 50 and 100] for 48 hrs at 37 degree C. A dose of 100 MuM was selected that induces a 50% inhibition in the cell growth calculated by MTT and morphometery assays. The result shows that in the presence of piperine neurite outgrowth was decreased in a dose dependent manner. The gene expression of TN-C, TNfnD and TnfnC were significantly reduced whereas the expression intensities of TnfnA1, TnfnA2, CSPGs and Laminin were significantly elevated when compared to their respective untreated controls. Similarly proinflammatory marker COX-2 expression was significantly inhibited in the presence of piperine when compared to untreated controls. This is the first time we have illustrated that irrespective of increased expressions of CSPGs, a significant reduction in Tenascin-C and its TNfnD and TNfnC domains are necessary to inhibit the tumor progression. Taken together, the capabilities of piperine to induce an apoptosis by decreasing the neurite outgrowth, proliferation rate and expression of TN-C and COX-2 in Neuro-2a cell line confirmed for its anticancerous and anti-inflammatory potential

Role of Pancreatic Stent placement in prevention of post Endoscopic retrograde Cholangiopancreatography Pancreatitis: experience at a tertiary care hospital in Pakistan

Objective: To determine the frequency of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis [PEP] in patients who underwent prophylactic pancreatic duct stenting

Study Design: Descriptive case series

Place and Duration of Study: This descriptive case series was conducted at the department of Gastroenterology, Pak Emirates Military Hospital Rawalpindi, from Jul 2017 to Feb 2018

Material and Methods: One hundred and twenty consecutive patients were enrolled after they met inclusion and exclusion criteria. Endoscopic Retrograde Cholangiopancreatography Pancreatitis [ERCP] was performed by Olympus duodeno scope [TJF Q180V] by an endoscopist having at least 3 years experience of performingindependent ERCPs. An additional 4, 6, or 7cm long 5FrGeenen[registration sign] pancreatic plastic stent [Cook Medical] was placed in all cases where pancreatic duct was accidentally cannulated. Primary outcome variable was post ERCP pancreatitis. Data was recorded on a pre-designed proforma and analyzed by SPSS version 21.0

Results: Out of total 120 cases, PEP was found in 4 [3.3 percent] patients. All the 4 patients had mild pancreatitis

Conclusion: PEP is not an uncommon complication following ERCP. The rate of PEP appears to be lower with prophylactic pancreatic duct stenting

Comparison of efficacy and safety of topical betamethasone valerate 0.1 percent with narrowband-UVB in atopic dermatitis

Objective: To compare the efficacy and safety of topical betamethasone valerate 0.1 percent with narrowband ultraviolet B [NB-UVB] therapy in atopic dermatitis

Method: Sixty patients with AD fulfilling the inclusion criteria were entered in the study. Patients were divided into 2 groups. Group A were given betamethasone valerate 0.1 percent twice a day for 4 weeks. Group B were given NB-UVB thrice a week for 8 weeks. Starting dose was 75 percent of minimal erythema dose [MED] for the skin type III and IV. Dose was increased by 20 percent on each visit as tolerated by the patients. During treatment patients were assessed at 2[nd]and 4[th]week for betamethasone valerate and 2[nd], 4[th], 6[th] and 8[th]week for NB-UVB

Results: 84 percent patients in group A [betamethasone] showed >50 percent reduction in Scoring of Atopic Dermatitis [SCORAD] whereas 94 percent patients in group B [NB-UVB] showed >50 percent reduction in SCORAD [p=0.554]. Side effects were seen in 34 percent patients in group A and 20 percent in group B

Conclusion: Both betamethasone valerate 0.1 percent and NB-UVB are almost equal in terms of efficacy but NB-UVB is more safe than betamethasone valerate 0.1 percent

Female pseudohermaphroditism: Congenital adrenal hyperplasia presenting with diffuse hyperpigmentation

The term congenital adrenal hyperplasia [CAH] comprises a group of autosomal recessive disorders, each of which involves a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both. The clinical presentation varies according to chromosomal sex. The sex of neonate with CAH is often initially unclear because of genital ambiguity. We report a case of 25-year-old phenotypically male, presenting with generalized hyperpigmentation for 5 years and occasional syncope for 1 year. On examination there were sparse axillary and pubic hair with ambiguous genitalia. 46XX karyotype, hypoplastic uterus on CT scan and elevated ACTH and 17-hydroxyprogesterone levels lead to the diagnosis of female pseudohermaphroditism due to congenital adrenal hyperplasia and patient was started on glucocorticoids and fludrocortisone by endocrinologist and was also referred to plastic surgeon

Neurite outgrowth properties of calotropis procera: In search for a neuroprotectant

In view of the well-documented medicinal properties of Calotropis procera [CP], the present study was designed to evaluate the neuroprotective effect of the extract. We have prepared a methanolic extract of Calotropis procera and screen varying concentration of CP [20, 30, 40, 50 and 70microg/ml] for the stimulatory potency on neurite outgrowth. The stimulatory effect of CP on neurite outgrowth was assessed in primary hippocampal neurons. Neurite lengths were measured using optika provison analysis software. Neuritogenesis was further analyzed by immunostaining by using specific neuronal marker beta III-tubulin. The data show that neurite outgrowth from hippocampal neurons were significantly enhanced in the presence of CP [40microg/ml]. The most stimulatory neurite outgrowth effects were appeared after 48hrs incubation of neurons with CP [40microg/ml]. These data confirm that CP extract could promote invitro hippocampal neurite outgrowth in a dose-dependent manner. Our results indicate that CP can be used as a healthy dietary supplement for the cognitive functions of the brain

Vitex negundo induces an anticonvulsant effect by inhibiting voltage gated sodium channels in murine Neuro 2A cell line

Vitex negundo [Vn] extract is famous for the treatment of neurological diseases such as migraine and epilepsy. These neurological diseases have been associated with abnormally increased influx of sodium ions into the neurons. Drugs that inhibit voltage gated sodium channels can be used as potent anti-epileptics. Till now, the effects of Vn on sodium channels have not been investigated. Therefore, we have investigated the effects of methalonic fraction of Vn extract in Murine Neuro 2A cell line. Cells were cultured in a defined medium with or without the Vn extract [100 microg/ml]. Sodium currents were recorded using whole-cell patch clamp method. The data show that methanolic extract of Vn inhibited sodium currents in a dose dependent manner [IC50 =161microg/ml]. Vn [100 microg/ml] shifted the steady-state inactivation curve to the left or towards the hyper polarization state. However, Vn did not show any effects on outward rectifying potassium currents. Moreover, Vn [100 microg/ml] significantly reduced the sustained repetitive [48 +/- 4.8%, P<0.01] firing from neonatal hippocampal neurons at 12 DIV. Hence, our data suggested that inhibition of sodium channels by Vn may exert pharmacological effects in reducing pain and convulsions

Neuroprotective capabilities of Vitex negundo in primary hippocampal neurons

Vitex negundu [Vn] is a well-known aromatic shrub commonly used as a traditional folk medicine famous for its potential pharmacological and biological activities. Several chemical compounds are extracted and identified from the different parts of the Vn such as leaves, root, seeds and flowers. Number of researches reported the herb as antimicrobial, anti-androgenic, anti-osteoporotic, and anti-tumour, anti-cancer, anti-inflammatory, anti-oxidant, anti-hyperglycemic and hepatoprotective. The effects of Vn on neurite outgrowth have not been identified till now. Therefore present study was designed to investigate the neurite outgrowth effects of Vn extract in hippocampal neurons. Neurons from P0 mice were isolated and cultured in defined medium containing the different concentrations of Vn [20, 30, 40, 50, 100, 150 and 200 microg/ml] for 48 hrs. The presence of the neurites was confirmed by using betaIII-tubulin antibody which specifically labels only the neurites. Morphometric analysis was done by using Optika Pro-Vision software. The data show that Vn at 30 and 40 microg/ml significantly increased the mean average length of the longest neurite whereas at 150 and 200 microg/ml it significantly decreased the mean average length of the 10 longest neurite in hippocampal neurons. Nevertheless Vn did not show any significant effects on the sum of all the neurite lengths at any concentrations tested. Taken together the result shows that methanolic extract of Vn has potential to produce long neurites at 30 and 40 microg/ml and therefore can be act as a neuroprotective agent in the future drug development

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.

A second reported malignancy in a patient with Morquio syndrome

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidneys.

Efficacy of sclerotherapy with sodium tetradecyl sulphate in the treatment of pyogenic granuloma

Objective: To determine the efficacy of sclerotherapy in treating pyogenic granuloma

Methods: The present study was conducted at outpatient Department Dermatology, Unit I, Mayo Hospital, Lahore. 35 patients were enrolled and were injected with 0.1ml of 3% sodium tetradecyl sulfate with the help of an insulin syringe, without local anesthesia, till the point of blanching. Patient was called weekly for two weeks for follow up to see clearance of the lesion and then after 3 months to see any recurrence using a caliper

Results: The mean age of the patients was 28.48 +/- 11.64 years. 42.9% patients were males and 57.1% patients were females. Complete clearance of lesion was found in 30 [85.7%] patients whereas 2 [5.7%] patients showed no reduction

Conclusion: Sclerotherapy is an effective procedure for the treatment of pyogenic granuloma patients

Comparison of efficacy of intralesional 5-fluorouracil plus triamcinolone acetonide versus intralesional triamcinolone acetonide in the treatment of keloids

Objective: To compare efficacy of intralesional 5-fluorouracil [5-FU] plus triamcinolone acetonide [TCA] versus intralesional TCA alone in the treatment of keloids

Methods The study included 100 patients with keloids. Patients were divided into two groups. Randomization was done through lottery method. For each 1 cm area, group A was given intralesional 5-FU 50 mg/ml [0.9ml] plus TCA 40mg/ml [0.1ml] after every 4 weeks and group B was given intralesional TCA 40mg/ml [0.1ml] after every 4 weeks for total period of 12 weeks. Administration of the drugs was continued till the keloid flattened or for a maximum period of 12 weeks. Follow-up was done every 4 weeks for total period of 12 weeks after the administration of last injection. Decrease in total score using Vancouver Scar Scale was calculated

Results: After the completion of study mean reduction in Vancouver Scar Score was -71.18 +/- 8.69 in the intralesional 5-FU plus TCA group as compared to -50.80 +/- 8.59 in the intralesional TCA group [p=0.001]. 5-FU + TCA was efficacious in 98% of cases [group A] and TCA alone in 62% of cases [group B]. No serious adverse effects were noticed in either group

Conclusion: Intralesional 5-FU plus TCA is significantly better than intralesional TCA alone in the treatment of keloids