A Unique Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene Causing Cystic Fibrosis in a Pakistani Child: A Case Highlighting the Need for More Awareness.

Cystic fibrosis (CF) is a recessively inherited disease most commonly seen in Caucasians. The mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for the condition, and to date, more than 2000 mutations have been published in the literature. The most common mutation worldwide is F508del. Here, we reported a five-year-old child who presented to the clinic with a chronic cough. Her newborn screening for CF was negative, including 139 mutation panels done in India. The sweat chloride test was positive, and CF gene sequencing was reported as c.2489dup p. (Glu831GLYFS *5) homozygotes mutation in the CFTR gene (Online Mendelian Inheritance in Man (OMIM) *602421). To the best of our knowledge, this gene was first described and published in the literature.

A Case of Coexistent Sarcoidosis and Tuberculosis: A Diagnostic Dilemma.

Sarcoidosis and tuberculosis (TB) are chronic granulomatous diseases with similar radiological, clinical, and histopathological presentations. Although rare, both conditions can coexist together. Case reports of concomitant incidence have been published in the literature. The classic manifestations of both diseases overlap, making it difficult for clinicians to reach a final diagnosis. While TB is responsible for the majority of necrotizing granuloma cases, necrotizing sarcoidosis should be considered a possible diagnosis, especially in the absence of mycobacterial antigen isolation or when a remarkable improvement isn't achieved after administering anti-tb medications. We report a rare case of a 12-year-old female exhibiting an atypical form of the granulomatous disease (concomitant incidence of tuberculosis and sarcoidosis), who presented with respiratory distress, cough, fever, weight loss, and generalized fatigue that was initially diagnosed as Tuberculosis which was supported by radiological and biological findings. Initially, the patient had shown some clinical improvement with anti-tubercular treatment, but nonetheless, she experienced progressively increasing mediastinal lymphadenopathy. Subsequently, she developed new granulomatous skin findings. Further investigations supported the diagnosis of coexisting sarcoidosis.

Subcutaneous Fat Necrosis of the Newborn After Whole-Body Cooling for Birth Asphyxia.

Therapeutic hypothermia (TH) is a challenging treatment for a neonate who suffers from hypoxic-ischemic encephalopathy. It has been shown to improve neurodevelopmental outcomes and survival in infants with moderate-to-severe hypoxic-ischemic encephalopathy. However, it has severe adverse effects such as subcutaneous fat necrosis (SCFN). SCFN is a rare disorder that affects term neonates. It is a self-limited disorder but can have severe complications such as hypercalcemia, hypoglycemia, metastatic calcifications, and thrombocytopenia. In this case report, we present a term newborn who developed SCFN after whole-body cooling.

Beyond the Local Basic Panel: Full CFTR Gene Analysis Identifies Novel CF Mutation Missed on Standard Testing in an Arabic Child.

Cystic fibrosis (CF) is an autosomal recessive disease caused by different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is the most common inherited disorder in the Caucasian population, with around 2000 mutations identified for the CFTR gene. The precise prevalence of CF in Arab countries remains unknown, with the prevalence of F508 del found to be a common type with other endemic mutations. We describe the case of a CF patient who was diagnosed at the age of seven years. She presented post-cardiac surgery for further evaluation for a recurrent chest infection and subtle dysmorphic features. CF genetic testing for the most common 31 mutations (CF panel) was negative, and a novel mutation was identified on CFTR gene sequencing.

A Retrospective Chart Review of Pediatric Complicated Community-Acquired Pneumonia: An Experience in the Al Qassimi Women and Children Hospital.

Background Community-acquired pneumonia (CAP) is one of the most common global health issues. Even though many vaccinations and new diagnostic tools are available, CAP has a higher mortality rate, especially in children less than five years of age. Complicated CAP (CCAP) in a healthy child is a severe disease characterized by a combination of local complications, such as parapneumonic effusion (PPE), empyema (EMP), necrotizing pneumonia (NP), abscess, pneumothorax, and bronchopleural fistula, and systemic complications, such as bacteremia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and, rarely, death. This study describes the demographic features, clinical presentation, management, and outcomes of patients diagnosed with CCAP at the Al Qassimi Women's and Children's Hospital (AQWCH). Methodology This retrospective chart review aims to collect and explore the data of all previously healthy children admitted with CCAP between the ages of one month and 13 years at AQWCH from January 2018 to December 2020. The primary study outcome measure is to provide clinicians with the diagnostics, evaluation, and management required to treat complicated pneumonia. Results A total of 195 patients were diagnosed with CAP, of whom 30 (15.3%) were diagnosed with CCAP. Of these, 14 (46.6%) patients had NP, eight (26.7%) had PPE, and eight (26.7%) had EMP. The median age of patients was 2.5 years, with 13 (43%) males and 17 (57%) females. The median duration of their stay in the hospital was 16 days. All patients were vaccinated with Hib, PCV13, or PCV7, and 57% of the patients received antibiotics before admission. The most common findings were consolidation and pleural effusion. Blood culture was negative in all cases, and pleural culture was positive only in three cases. A total of 17 (57%) patients underwent video-assisted thoracoscopic surgery (VATS), and post-VATS surgical emphysema was found to be the most common complication. Chest X-rays normalized after three months in 65% of patients. On comparing patients who were admitted to the Pediatric Intensive Care Unit (PICU) before any surgical intervention with those who were not, it was found that patients who required PICU admission were young (median = 2 years; interquartile range (IQR) = 1-4.5; p = 0.044) and had higher respiratory rate (mean = 49 breaths/per minute, standard deviation (SD) = 11; p = 0.000). In addition, they had lower median albumin (median = 2 g/L; IQR = 1.8-2.23; p = 0.004). On comparing patients who required VATS and those who did not require VATS, it was found that the former had a higher median respiratory rate (48 per min; range = 42-54; p = 0.01). A cavity in the chest computed tomography (CT) was found in 86% of patients with VATS (p = 0.017), and they had lower median albumin (median = 2 g/L; IQR = 1.92-2.24; p = 0.012), as well as longer median duration of using oral antibiotics (median = 21 days; IQR = 19-26; p = 0.025). Patients with complicated NP had a higher respiratory rate and higher PICU admission, and more cavity in the chest was found in the CT study. Most NP patients also underwent VATS and had longer median days of using oral antibiotics. One patient developed a bronchopleural fistula, and one patient diagnosed with NP died. Conclusions CCAP is a major cause of hospitalization in children. It is important to suspect CCAP in all CAP patients not responding to treatment after 48-72 hours.

Metastatic colorectal cancer in both sides of Aegean sea: practice patterns and outcome.

OBJECTIVE: The successful results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients in real life. This multinational registry study aimed to evaluate the real-life data effecting the survival of patients with mCRC. METHODS: This is a multinational, retrospective registry study. Turkish and Greek mCRC patients diagnosed between 2005 and 2012, with at least 3 years of follow-up data or who died before 3 years of follow-up were included in the study. RESULTS: A total of 364 were included in the study. RAS and BRAF mutation rates were found to be 36% and 39%, respectively. As first-line therapy, 196 (54%) patients received bevacizumab and Anti-EGFR treatments in combination with chemotherapy. The objective response rate was 42% (n = 152) and 32% (n = 78) for 1st line and 2nd line treatments, respectively. While the median progression-free survival (PFS) with the 1st line treatment was 10 months, it was 7 months with the 2nd line treatments. In the total study population median PFS and overall survival (OS) were 10 (95% CI, 8.3-11.6) and 35 (95% CI, 30.7-39.2) months, respectively. In Turkish and Greek patients, median OS (36 months versus 29 months, p = .81) and PFS (10.2 versus 9.2, p = .42) were not different. In multivariate analysis, ECOG PS of ≥2 and having metastases in more than one region decreased overall survival (p = .002 and p = .003), it was found that wild RAS and BRAF mutations and second metastasectomy contributed to overall survival (p = .047 and p < .001). CONCLUSION: In conclusion, it seems that the patient's performance status, tumor location, number of metastatic lesions at the time of diagnosis affect the prognosis of mCRC. Although access to molecular tests and first-line treatments differ between Greece and Turkey, no significant difference was found in survival times.

Pulmonary Arterial Hypertension as a Fatal Complication of Neurofibromatosis Type 1 in a Neonate: A Diagnostic Dilemma.

Neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is a genetically transmitted autosomal dominant disease, with a prevalence of one per 4000 live births. Pulmonary arterial hypertension (PAH) is a rare but potentially life-threatening complication of NF1. There are no confirmatory data about the congenital association between PAH and NF1. However, in most cases, PAH is observed in late childhood or adulthood. Herein, we present a preterm baby with genetically confirmed NF1 who presented with PAH.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Bilateral Pulmonary Langerhans's Cell Histiocytosis is Surgical Challenge in Children: A Case Report.

Background Pulmonary Langerhans's cell histiocytosis (PLCH) is a rare cause of interstitial lung disease in children and more than half of the cases are bilateral. Persistent respiratory distress due to spontaneous pneumothorax (SP) in bilateral PLCH may refractory to conservative treatment and posed a great challenge to surgical modalities. A 3-year-old boy with SP due to bilateral PLCH is presented to discuss the surgical options of recurrent and refractory PLCH cases in children. Case Report The patient was admitted to the emergency department with severe respiratory distress and SP. After chest tube insertion, biopsy from neck mass revealed Langerhans's cell histiocytosis. Chemotherapy including vinblastine and prednisone was initiated. Due to persistent respiratory difficulty and air leaks, talc pleurodesis and thoracoscopic bullae excision with pleural decortication were performed. Two months after the admission, due to nosocomial infection and severe respiratory distress, extracorporeal membranous oxygenation (ECMO) support was initiated. The patient was died of ECMO complications on 24th day of ECMO. Conclusion Despite the use of chemotherapy and surgical excision of cystic lesions, bilateral PLCH in children may have lethal outcome. Other treatment options including respiratory support with ECMO and lung transplantation should be considered as last resort of treatment alternative in persistent cases.

Correlation between 18F-FDG Positron-Emission Tomography 18F-FDG Uptake Levels at Diagnosis and Histopathologic and Immunohistochemical Factors in Patients with Breast Cancer.

OBJECTIVE: In this study, we aimed to determine the correlation between pretreatment-staging 18F-FDG total body positron-emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) levels and histopathologic and immunohistochemical predictive and prognostic factors in patients with breast cancer. MATERIALS AND METHODS: One hundred thirty-nine women with breast cancer who were treated between 2009 and 2015 at our hospital and who had pretreatment-staging PET/CT were included in the study. SUVmax levels and histopathologic and immunohistochemical results were compared. RESULTS: The median age was 48 years (range, 29-79 years). The mean tumor diameter was 33.4 mm (range, 7-120 mm). The histology was invasive ductal carcinoma in 80.6% of the patients. In the univariate analysis, SUVmax levels were significantly higher in patients with invasive ductal carcinoma; in patients with a maximum tumor diameter more than 2 cm; patients who were estrogen, progesterone, and combined hormone receptor-negative, triple-negative patients, and in tumors with higher grades (p<0.05). In HER2-positive patients, SUVmax levels were higher even if it was not statistically significant. There was no correlation between lymph node metastases and pathologic stage. In multivariate analysis, tumor diameter was an independent factor. CONCLUSION: SUVmax levels are correlated with known histopathologic and immunohistochemical prognostic factors. PET/CT could be useful in preoperative evaluation of patients with breast cancer to predict biologic characteristics of tumors and prognosis.

Thymoma with immunodeficiency with multiple recurrent oral herpetic infections.

Thymomas with immunodeficiency (formerly Good's syndrome) are a rare acquired disease of combined T- and B-cell immunodeficiency accompanying a thymoma. Recurrent opportunistic infections associated with disorders of both humoral and cell-mediated immunity frequently accompany this rare primary, adult-onset immunodeficiency. This is a report of a case of a thymoma with immunodeficiency in a 65-year-old male patient who developed recurrent oral herpetic infections. He consulted us about recurrent vesiculo-ulcerative lesions on his tongue, lower lip, and buccal mucosa. Results of laboratory examinations indicated hypogammaglobulinemia accompanied by diminished B cells in the peripheral blood, which is consistent with the characteristic features of a thymoma with immunodeficiency. After a diagnosis confirming herpes simplex virus infection, systemic antiviral therapy was administered, which was effective for his vesiculo-ulcerative lesions at follow-up. When an intractable infection accompanied by a thymoma is encountered, increased awareness about the clinical and immunological profiles of this primary immunodeficiency may help in its early diagnosis, thereby preventing mortality.

Primary pericardial extragastrointestinal stromal tumor: A case report and literature review.

Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal tumors of the gastrointestinal tract. GISTs are considered to originate from the interstitial cells of Cajal, the pacemakers of the peristaltic activity of the gastrointestinal tract. More than 95% of GISTs express KIT protein and discovered on GIST-1. GISTs may also be encountered in locations outside the gastrointestinal tract, in which case they are referred to as extra-GISTs (EGISTs) and often behave more aggressively. This is the case report of a primary pericardial EGIST in a 53-year-old male patient, confirmed by immunohistochemistry. To the best of our knowledge, this is the third case of EGIST diagnosed above the diaphragm, without being associated with the esophageal wall. Two cases of primary EGIST arising from the pleura were reported previously. In addition, this is the first reported case of an EGIST originating from the pericardium.

Clinical comparison of submucosal injection of dexamethasone and triamcinolone acetonide on postoperative discomfort after third molar surgery.

OBJECTIVE: The aim of the study was to compare the effect of submucosal injection of dexamethasone and triamcinolone acetonide on postoperative pain, swelling, and trismus occurring after impacted mandibular third molar surgery. METHOD AND MATERIALS: A total of 78 patients (aged 18 to 35) with asymptomatic, unilateral, impacted mandibular third molar, and without any systemic disease were included in this study. Patients were divided into three groups randomly (control, dexamethasone, and triamcinolone acetonide). In the experimental groups, dexamethasone and triamcinolone acetonide were injected into submucosa at about 1 cm above the surgical area submucosally. The control group of patients did not take any drug submucosally but the same surgical procedure was applied. Pain evaluation was performed by visual analog scale (VAS). Swelling was measured using a flexible standard ruler measuring the dimensions of the axes between certain points on the face. For trismus evaluation, maximum mouth opening was measured. Measurements taken on the preoperative, and on postoperative first, third, and seventh days were compared with each other and statistically evaluated. RESULTS: There were statistically significant differences between the control and experimental groups on the different days of the postoperative period. The effect of triamcinolone acetonide on pain started on the first day postoperatively and the effect of triamcinolone acetonide on trismus and pain was better than other groups at the third and seventh days. However, there was no statistically significant difference between the effects of dexamethasone and triamcinolone acetonide regarding postoperative complications. CONCLUSION: The submucosal injection of dexamethasone or triamcinolone acetonide might be an effective treatment for postoperative discomfort occurring following impacted mandibular third molar surgery, and triamcinolone acetonide could be applied as an alternative to dexamethasone.

Staging with PET-CT in patients with locally advanced non small cell lung cancer is superior to conventional staging methods in terms of survival.

BACKGROUND: Of patients with non small cell lung cancer (NSCLC), around one third are locally advanced at the time of diagnosis. Because only a proprotion of stage III patients can be cured by surgery, in order to improve the outcomes, sequential or concurrent chemoradiation, or concurrent chemoradiation with induction or consolidation is offered to the patients with locally advanced NSCLC. Today, PET combined with computerized tomography (PET-CT) is accepted as the most sensitive technique for detecting mediastinal lymph node and extracranial metastases from NSCLC. We aimed to compare PET-CT and conventional staging procedures for decisions regarding curative treatment of locally advanced NSCLC. MATERIALS AND METHODS: A total of 168 consecutive patients were included from Acibadem Kayseri Hospital, Acibadem Adana Hospital and Kayseri Research and Training Hospital in this study. RESULTS: While the median PFS was 13.0 ± 1.9 months in the PET-CT group, it was only 6.0 ± 0.9 in the others (p<0.001). The median OS values were 20.5 ± 15.6 and 11.5 ± 1.5 months, respectively (p<0.001). DISCUSSION: As a result, we found that staging with PET CT has better results in terms of survival staging. This superiority leads to survival advantage in patients with locally advanced NSCLC.

False Positive 18F-FDG Uptake in Mediastinal Lymph Nodes Detected with Positron Emission Tomography in Breast Cancer: A Case Report.

Breast cancer is the most frequently diagnosed cancer among females. It is accepted that lymph node involvement with metastatic tumor and the presence of distant metastasis are the most important prognostic factors. Accurate staging is important in determining prognosis and appropriate treatment. Positron emission tomography with computed tomography detects malignancies using 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG PET CT) with high accuracy and they contribute to decisions regarding diagnosis, staging, recurrence, and treatment response. Here, we report a case of false positive metastatic mediastinal lymph nodes that were diagnosed by 18F-FDG PET CT in a 40-year-old breast cancer patient who had undergone preoperative evaluation. Right paratracheal, prevascular, aorticopulmonary, precarinal, subcarinal, hilar, and subhilar multiple conglomerated mediastinal lymph nodes were revealed in addition to left breast mass and axillary lymph nodes. Mediastinoscopy was performed with biopsy and pathology was reported as granulomatous lymphadenitis. In conclusion, any abnormal FDG accumulation in unusual lymph nodes must be evaluated carefully and confirmed histopathologically.

Sunlight may increase the FDG uptake value in primary tumors of patients with non-small cell lung cancer.

Currently, positron emission tomography with computerized tomography (PET-CT) is the most sensitive technique for detecting extracranial metastases in non-small cell lung cancer (NSCLC). It has been reported that there is a correlation between the maximal standardized uptake value (SUV(max)) of primary tumors and prognosis in patients with NSCLC. The effect of sunlight exposure on PET-CT SUV(max) value is not known. Therefore, we aimed to evaluate the effect of sunlight exposure on PET-CT SUV(max) value in patients with NSCLC. A total of 290 patients with NSCLC from two different regions of Turkey (Kayseri, n=168 and Adana, n=122) that have different climate and sunlight exposure intensity, were included in the study. Age, gender, histology of cancer, cancer stage, smoking status, comorbidity and SUV(max) of the primary tumor area at the time of staging were evaluated as prognostic factors. In the multivariate analysis, we detected that the region was the only independent factor affecting SUV(max) (P=0.019). We identified that warmer climate and more sunlight exposure significantly increases the SUV(max) value of the primary tumor area in patients with NSCLC. Further studies are warranted to clarify the issue.

Maxillary ameloblastoma mimicking an oroantral fistula.

BACKGROUND: The aim of this current report is to present an unusual case of a maxillary ameloblastoma mimicking an oroantral fistula. CASE REPORT: A left subtotal maxillectomy via Weber-Ferguson-type incision was performed. The patient tolerated the procedure well, the postoperative course was uneventful, and the patient was discharged 3 days after surgery with a mild paraesthesia of the right infraorbital nerve distribution. The infraorbital nerve paraesthesia has resolved 5 months after resection. The patient has been followed-up for 3 years without recurrence. DISCUSSION: Ameloblastoma is a well-known pathology of the maxillofacial region. However, unusual manifestations of this tumor can represent a serious challenge for diagnosis.

Histological evaluation of the changes in temporomandibular joint capsule and retrodiscal ligaments following autologous blood injection.

INTRODUCTION: In recent years injection of autologous blood into the temporomandibular joint (TMJ) has been reintroduced as a treatment of chronic recurrent TMJ dislocation. The effects of this treatment on components of the TMJ is not fully understood. The purpose of this article is to evaluate the effects of autologous blood on TMJ capsule and the retrodiscal ligament. MATERIAL AND METHODS: A total of 16 healthy adult country bred pig were used in this study. Autologous blood were injected into the upper joint space (4 ml) and around the capsule of TMJ unilaterally (1 ml). This procedure was then repeated on the opposite side only by using 5 ml of 0.9% saline. TMJ capsules and retrodiscal ligaments were examined four weeks following the injections. RESULTS: Histological examination of TMJs injected with autologous blood revealed fibrotic changes in 81.25% of the retrodiscal ligaments and 56.25% of the capsular areas. Whilst no changes were seen in the retrodiscal ligaments nor in the capsules of TMJs injected with saline alone. CONCLUSION: There is little published clinical data on the use of autologous blood injection and as such the mechanism of action is still unclear. The rate of induction of fibrosis within the retrodiscal ligaments in this study were similar to previously reported studies and case series. However, further studies to evaluate the mechanism of this safe and simple technique are needed.

Does sunlight exposure improve survival in patients with non-small cell lung cancer?

BACKGROUND: Some epidemiological studies reported that sunlight exposure and highvitamin D levels may decrease the morbidity and mortality related to cancer. We aimed to evaluate whether sunlight exposure has an impact on survival in patients with non small cell lung cancer. MATERIALS AND METHODS: A total of 546 patients with NSCLC from two different regions (Kayseri and Adana) differing according to sunlight exposure were analysed retrospectively. RESULTS: The median overall survival (OS) rates were 11. 6 (CI: 9.50-13.6) and 15.6 months (CI: 12.4-18.8) for Kayseri and Adana, respectively, in all patients (p=0.880). CONCLUSIONS: There were no differences between groups in terms of OS. While there is strong evidence regarding inverse relationship between cancer incidence and sunlight exposure, it is still controversial whether sunlight exposure is a good prognostic factor for survival in patients with lung cancer.

Histomorphometric analysis of new bone obtained by osteogenic periosteal distraction in ovariectomized rabbits.

OBJECTIVE: The aim of this study was to evaluate the effects of estrogen deficiency on newly formed bone obtained by osteogenic periosteal distraction histomorphometrically. STUDY DESIGN: Thirty-six female rabbits were divided into 2 groups. The experimental group underwent a bilateral ovariectomy and a sham operation was applied to the control group to equalize the stress of ovariectomy surgery. Four weeks postoperatively, a gradual distraction of the mandibular corpus was performed. RESULTS: In the experimental group, callus formation was delayed and the new bone was less mineralized; conversely, when histomorphometric measurements were compared statistically, there were no significant differences between the ovariectomized and sham-operated subgroups in the mean extent of newly formed bone tissue. CONCLUSIONS: Although osteoporosis caused by the lack of estrogen has negative effects on osteogenic periosteal distraction (OPD), these negative effects do not appear to present a contraindication to OPD.