Umbilical Catheter Extravasation Mimicking Necrotizing Enterocolitis in a Preterm Neonate: A Diagnostic Challenge.

Managing acute abdomen in very low birth weight (VLBW) and premature infants presents a diagnostic challenge, often necessitating a thorough assessment to discern underlying causes. Umbilical venous catheters (UVCs), commonly used in neonatal intensive care, are essential but not without risks. A 29-week premature male infant, born to a 23-year-old mother, was referred to our clinic on the 16th day of life with a suspected diagnosis of necrotizing enterocolitis (NEC). The infant had spent the first day intubated and received non-invasive respiratory support for 15 days. A 5 French UVC was inserted at the 2nd hour of life, and by the 3rd day of life, the infant transitioned to minimal enteral feeding. Between the 12th and 16th days of life, the infant initially diagnosed with NEC due to symptoms such as decreased stool passage and abdominal distension. The patient had been on a continuous course of antibiotic treatment throughout the entirety of his life, commencing on the very first day due to suspected early neonatal sepsis, followed by nosocomial sepsis during the hospitalization, and persisting with antibiotic therapy for suspected NEC. The case took a unique turn upon further evaluation after being referred to our unit. Despite a preliminary NEC diagnosis, further evaluation revealed umbilical catheter complications, leading to total parenteral nutrition extravasation. Removal of the catheter, drainage, and antibiotic adjustment resulted in improved clinical outcomes. In neonatal care, cautious management is vital when dealing with infants exhibiting abdominal symptoms. A nuanced approach, including differential diagnosis and careful antibiotic use, is essential.

A New Perspective on the Pathogenesis of Infantile Colic: Is Infantile Colic a Biorhythm Disorder?

OBJECTIVES: In this study, we investigated the relationship between infantile colic, migraine, and biorhythm regulation, by evaluating biochemical and molecular parameters. STUDY DESIGN: Healthy infants with and without infantile colic were eligible for this prospective cohort study. A questionnaire was applied. Between the 6th and 8th postnatal weeks, day and night circadian histone gene H3f3b mRNA expression and spot urine excretion of serotonin, cortisol, and 6-sulphatoxymelatonin were analyzed. RESULTS: Among the 95 infants included, 49 were diagnosed with infantile colic. In the colic group, defecation difficulty, sensitivity to light/sound, and maternal migraine frequency increased and sleep disruption was typical. In the melatonin analysis, the difference between day and night levels was significant in the control group, indicating an established circadian rhythm ( P = 0.014). In the colic group, there was no day-night difference ( P = 0.216) in melatonin, but serotonin levels were higher at night. In the cortisol analysis, day-night values were similar in both groups. Day-night variability of H3f3b mRNA levels between the groups was significant, indicating circadian rhythm disturbance in the colic group compared to the control group ( P = 0.003). Fluctuations in circadian genes and hormones expected in healthy rhythm were revealed in the control group, but were missing in the colic group. CONCLUSION: Due to the gaps in the etipathogenesis in infantile colic, a unique effective agent has not been discovered so far. This study, which demonstrated for the first time that infantile colic is a biorhythm disorder using molecular methods, fills the gap in this regard and points to a completely different perspective in terms of treatment.

[Autophagy Markers Induced by Influenza Virus and MUC1 Expressions in Cancer-Derived Cell Lines]. / Kanser Kökenli Hücre Dizilerinde Influenza Virüsünün Indükledigi Otofaji Belirteçleri ile MUC1 Ekspresyonu Arasindaki Iliskinin Arastirilmasi.

Influenza virus-induced autophagy is often accompanied by apoptosis and results in cell death in virus-infected cells. It is well known that autophagy is modulated by the mTOR/PI3K/Akt pathway, which plays an important role in the response to the presence of energy sources and external stimuli. This pathway is modulated by mucin 1 (MUC1), which has extracellular and intracellular components and plays an important role in metastasis and chemotherapeutic resistance. In this study, it was aimed to investigate the expression of MUC1 after the inoculation of influenza viruses into the cancer-derived cell cultures and, accordingly, the changes in autophagy markers such as mTOR and LC3B. In this study, MCF-7, HeLa and A-549 cell lines were used which have adenocarcinoma origin. To control the growth of influenza virus in these cells, the MDCK cell line was also inoculated. Centrifuge-enhanced shell-vial cell culture method was used in all experiments. Influenza A (H1N1) pdm09 strain was inoculated into these cell lines then the expressions of viral nucleic acid and cycle threshold (Ct) of MUC1, mTOR, LC3B associated genes were investigated by quantitative real-time reverse transcriptase polymerase chain reaction (qRTPCR) method in the samples taken from the supernatants of all cells at the end of the 48-hour incubation period. To investigate whether these markers were present in cells, after all cells were permeabilized with paraformaldehyde, cell-coated infected coverslips were stained with fluorescent labeled monoclonal antibodies developed against MUC1, mTOR, LC3B and influenza virus antigens. In the examination of fluorescence microscopy, all of the cell cultures (MCF-7, He-La and A-549) infected with influenza virus yielded positive results in terms of LC3B, mTOR and MUC1 monoclonal antibody staining, whereas all of the non-infected cells were found negative. Cycle threshold values of MUC1, LC3B and mTOR associated genes were found to be lower in A-549 cell line inoculated with influenza virus. Although protein expression was demonstrated in MCF-7 and He-La cell lines, similar changes were not detected in the 1/Ct values of genes in the autophagy pathway. The Ct value of the MUC1 gene was found to be higher only in the MCF-7 cell line after inoculation. In conclusion, it was observed that the specific expression pattern for influenza virus-induced autophagy was formed only in the A-549 cell line among the adenocarcinoma cells. It was thought that this relationship could constitute a dataset in further research on lung adenocarcinoma. However, in future studies, the determination of the expression of these genes at the protein level by using further tests will provide better comparison of the results.

Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation in adult patients: Diagnosis, incidence, prophylaxis, and treatment.

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) affecting the liver is a rare, possibly life-threatening complication of hematopoietic stem cell transplantation (HSCT). Sinusoidal endothelial cell (SEC) damage triggered by various factors (especially conditioning regimen) results in post sinusoidal portal hypertension due to obstruction of the hepatic vein. Diagnosis is guided by traditional clinical diagnostic criteria; the modified Seattle criteria, the Baltimore and revised European Group for Blood and Marrow Transplantation (EBMT), specifically. While there are promising results of imaging techniques studies in the diagnosis of VOD/SOS, none of those imaging techniques are routinely utilized in diagnosis yet. However, risk stratification is essential; conflicting results have been shown in studies aiming to define risk factors for development of VOD/SOS conducted to date. The only approved drug for the treatment of VOD/SOS yet is defibrotide, with early treatment offering higher chances of survival. In this review, we will focus on pathogenesis, clinical presentation and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD/SOS occurring post-HSCT.

Transient elastography of liver: Could it be a guide for diagnosis and management strategy in hepatic veno-occlusive disease (sinusoidal obstruction syndrome)?

Hepatic veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS), is a rare and life threatening complication of hematopoetic stem cell transplantation (HSCT). Many conditions can mimic the clinical signs of VOD/SOS. Differential diagnosis and diagnosis of the disease at an early stage is important, since the severe form of the disease has higher mortality rates and early-initiated specific treatment has better response rates. A sensitive and specific non-invasive imaging technique that can diagnose the disease at an early stage is still an unmet need today. We aimed to determine the role of liver stiffness measurement (LSM) with transient elastograph (TE) for the diagnosis of VOD/SOS after allogeneic HSCT. Between January 2019 and October 2021, a total of 49 patients underwent allogeneic HSCT and were retrospectively analyzed. Thirty-one adult patients who had a two or more LSM value were included in the study. Revised European Society for Blood and Marrow Transplantation (EBMT) was the criteria used for the diagnosis of VOD/SOS. Two of 31 patients developed VOD/SOS (6.4 %). Very high LSM values were detected in all patients who developed VOD/SOS. Early and specific VOD/SOS treatment resulted in improvement of LSM values together with other related features. However, LSM values did not increase significantly in patients with high a bilirubin level (≥2 mg/dl) without VOD/SOS. This study demonstrates that TE might be a promising non-invasive imaging method for diagnosis, follow-up and differential diagnosis of this dismal complication of HSCT. Yet, these results need to be supported by prospective studies.

Extracorporeal photopheresis in the treatment of acute and chronic graft-versus-host disease: A position statement from the Turkish Society of Apheresis (TSA).

Graft versus host disease (GVHD) is still the most important cause of mortality and morbidity after allogeneic stem cell transplantation. Though perfect response rates are not achieved, steroids are still the first-line treatment. In the face of the presence of the drugs approved by FDA in recent years for acute and chronic GVHD as second-line therapy in the steroid-refractory group, there exists no standard approach. Extracorporeal photopheresis (ECP) with an immunomodulatory effect, is favored in the treatment of both acute and chronic steroid refractory GVHD as it does not increase the risk of relapses or infections. Having a low profile of side effects, ECP is also generally well-tolerated by patients. Being a time requiring procedure, the fact is that it is not able to be practiced in all health centers and requires central venous catheters in patients unfit for venous access may be enumerated among its shortcomings. No complete standard is available with respect to ECP application frequency-time; it varies from one center to another. The Turkish Society of Apheresis established the Turkish ECP (TECP) group and sought some answers to the questions regarding the use of ECP in the treatment of GVHD, and issued a position statement.

Natural History of Cirrhosis: Changing Trends in Etiology Over the Years.

BACKGROUND AND GOALS: The aims of the present study were to investigate the natural history of cirrhosis and to determine trends in the etiology of cirrhosis. METHODS: Between January 2001 and January 2018, a total of 1,341 patients had been diagnosed with cirrhosis and were included. RESULTS: A total of 898 cirrhotic patients, who were followed up for at least 6 months were included into the analysis. The median age was 54 years. The median Child-Pugh and MELD scores were 7.5 and 11, respectively. Ascites (51%) was the most common causes of decompensation. Chronic viral hepatitis was the most frequent cause of cirrhosis (58%). Hepatitis B virus (HBV) infection was the main etiology (34%), followed by hepatitis C virus (HCV) infection (18%). Among 129 patients with cryptogenic cirrhosis (CC), 60 had metabolic abnormalities. If these 60 patients with CC were considered to have nonalcoholic fatty liver disease (NAFLD)-related cirrhosis, the proportion of NAFLD-related cirrhosis increased from 1.8 to 8.0%. At admission, 74 patients (8%) had been diagnosed with hepatocellular carcinoma (HCC). A new HCC developed in 80 patients during the follow-up period. The probability of developing HCC was 3.9% at 12 months. Logistic regression analysis showed that the development of HCC was significantly associated with older age (p < 0.001), male gender (p < 0.001), viral etiology (p = 0.026), and baseline high aspartate aminotransferase level (p = 0.01). Overall, 104 cirrhotic patients died. CONCLUSION: HBV and HCV remain the leading causes of etiology in cirrhosis and HCC. However, NAFLD-related cirrhosis is recognized as a growing burden.

Role of Therapeutic Plasma Exchange in Guillain-Barre Syndrome after Allogeneic Hematopoietic Stem Cell Transplant: Report of Two Cases.

BACKGROUND: Guillain-Barre Syndrome (GBS) is an acute inflammatory polyneuropathy characterized with rapid, progressive, ascending, and symmetrical weakness and areflexia. It is supposed to be an autoimmune disease related with production of antibodies by T lymphocytes activated against antigenic proteins of the peripheral nerves. Guillain-Barre Syndrome occurring after hematopoietic stem cell transplant (HSCT) has been associated with viral infections or toxic effects of chemotherapy. METHODS: We report two GBS cases after HSCT treated successfully by means of therapeutic plasma exchange. RESULTS: In a total of 257 patients, 2 cases (0.8%) were diagnosed with GBS following HSCT. Allogeneic HSCT was performed and complete remission was achieved. Diagnosis of GBS was established on the 45th and 69th days with respect to clinical, cerebrospinal fluid, and electromyography findings. Patients did not respond to treatment consisting of intravenous immunoglobulins (IVIG) (1 g/kg/day) for 2 days and methylprednisolone (1 g/kg/day). Mechanical ventilation was indicated in one patient due to the involvement of respiratory muscles. Therapeutic plasma exchange resulted in complete recovery in both cases. CONCLUSIONS: Guillain-Barre Syndrome is a rare but serious complication, which may occur after HSCT. Increased awareness and early diagnosis are crucial in the management of GBS. First line treatment consists of IVIG and steroids and therapeutic plasma exchange must be considered without delay in refractory cases.

Current factors affecting the risk of omphalitis in newborns: A prospective case-control study.

AIM: We aimed to determine the current factors affecting the development of omphalitis in our region. MATERIALS AND METHODS: This prospective case-control study included term and late preterm newborns admitted to the newborn outpatient clinic or paediatric emergency service between 2014 and 2015. One hundred newborns with omphalitis and age-matched 100 newborns as a control group were included. The perinatal, postnatal, and sociocultural characteristics of newborns were evaluated and the factors that could influence the development of omphalitis were determined. RESULTS: Younger maternal age and primiparity, lower maternal education, and lower maternal hand washing habits were the significant risk factors of omphalitis development. Using non-cotton clothes were the most important risk factor amongst all factors as it increases the omphalitis risk up to 13 times. The frequency of omphalitis was significantly higher in warm months when microorganisms were able to colonise and reproduce compared with the colder months. CONCLUSION: Results suggested that community-based interventions promoting the improvement of neonatal care should emphasise simple and low-cost interventions such as hand washing habit of mothers, caring for the umbilical cord, and using cotton clothes for babies. This study also confirms the safety of dry cord care at the time of birth and afterwards. However, broadscale multicentric studies are needed to protect against omphalitis.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Revisiting post-gastrectomy anemia with a brief survey among a group of Turkish medical oncologists.

PURPOSE: Total or subtotal gastrectomy are performed as curative or palliative treatment in patients with gastric cancer. Anemia is a frequent complication of gastrectomy. Patients undergoing total or subtotal gastrectomy should be carefully monitored for the development of anemia and be given appropriate treatment when indicated. This survey-based study aimed to determine the level of knowledge about post-gastrectomy anemia in Turkish medical oncologists. METHODS: The study included 110 Turkish medical oncologists that agreed voluntarily to participate in the survey and answer an 8-item questionnaire. The survey was distributed as a questionnaire during the 5th Turkish Medical Oncology Congress in March 2014. RESULTS: All participants completed the questionnaire. Most of the participants would not recommend oral iron or cobalamin replacement after gastrectomy. CONCLUSION: The results of the survey indicate that Turkish medical oncologists have some knowledge about post-gastrectomy anemia, but need to learn more about appropriate follow-up and replacement therapies for post-gastrectomy anemia.

Chemomobilization with high-dose etoposide and G-CSF results in effective and safe stem cell collection in heavily pretreated lymphoma patients: report from a single institution study and review.

The optimal mobilization strategy prior to autologous stem cell transplantation (auto-SCT) for patients with lymphoma is yet to be determined. We reviewed our institutional experience using chemomobilization with high-dose (HD) etoposide (1.6 g/m(2) ) and G-CSF (300 µg/day) in 79 patients with lymphoma. The majority (76%) had received at least two prior regimens of chemotherapy, and 12 (15.2%) patients had previously failed to mobilize following HD cyclophosphamide or DHAP or ICE with G-CSF. HD etoposide and G-CSF chemomobilization resulted in successful collection (>2 × 10(6) CD34+ cells/kg) in 82.3% of patients within a median 2 (1-6) apheresis days. Patients had stem cells collected between days +8 and +15, with a median +12 day. Median total CD34+ cells/kg collected was 5.95 × 10(6) (0.1-36.8). Seventy-one percent of patients yielded >2 × 10(6) CD34+ cells/kg in ≤2 d of apheresis and were defined as good mobilizers. While median CD34+ cells/kg collected for good mobilizers was 7.6 × 10(6) , it was 2.6 × 10(6) for poor mobilizers (P < 0.001). This regimen was safe with a low rate of febrile neutropenia (7.6%) and acceptable rates of RBC (40.5%) and platelet transfusions (22.8%). Hematopoietic recovery after auto-SCT was achieved on expected time. Therapy-related myelodysplastic syndrome/acute myeloid leukemia occurred in only one patient (1.3%) with in a median follow-up of 16 months after chemomobilization. We conclude that HD etoposide and G-CSF chemomobilization appear to result in effective, tolerable, and safe stem cell collection in the majority of heavily pretreated lymphoma patients.

Assessment and comparison of acute cardiac toxicity during high-dose cyclophosphamide and high-dose etoposide stem cell mobilization regimens with N-terminal pro-B-type natriuretic peptide.

This study was undertaken to prospectively evaluate and compare the acute effect of high-dose (HD), cyclophosphamide (CY) and HD etoposide (ET) on cardiac function assessed by plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients undergoing stem-cell mobilization. NT-proBNP was measured at baseline and 6h after completion of mobilization chemotherapy (MC) in 58 patients. Of 58 patients, 33 received HD CY, and 25 received HD ET. The mean baseline NT-proBNP values were similar between the CY and ET group (119.5 vs 149, respectively, p>0.05). NT-proBNP levels were increased in almost all patients, except 2 from CY group. A significant difference between NT-proBNP concentrations at baseline and 6h after completion of MC was observed in both groups (p<0.001). The value of changes in NT-proBNP was more significant in the ET group. The changes in NT-proBNP according to the MC regimens were analyzed and a cut-off value of 422pg/ml was determined. Based on this cut-off value, only the type of MC was significantly correlated with the chances in NT-proBNP concentrations. Receiving HD ET as a MC was found to be 5.25 times more cardiotoxic compared to the HD CY. Congestive heart failure was seen in 3 (5.2%) patients. Our results suggest that stem cell mobilization with HD CY and HD ET cause acute cardiac toxicity mediated by neurohumoral activation, which was detected by the increases in cardiac biomarker NT-proBNP, and as a matter of fact cardiotoxicity of HD ET seems to be more potent than those exhibited by HD CY.

Granulocyte Transfusions in Neutropenic Infections: Insights From a Single-Center Study.

Introduction Despite the development of modern antibiotic and antifungal therapies, neutropenic infections remain life-threatening. Granulocyte transfusion (GTX) is a less frequently used treatment modality in patients with refractory neutropenic infections. The role of donor GTX remains controversial, partly because of the lack of proper clinical trials. This study aimed to contribute to the literature by evaluating the efficacy and side effects of granulocyte transfusions in our center. Methods Eight febrile neutropenic patients with confirmed infections received granulocyte transfusions from ABO-compatible related and unrelated donors. Donors received filgrastim and dexamethasone stimulation, and granulocyte suspensions were irradiated and administered within six hours. Monitoring, antibiotic therapy, and granulocyte colony-stimulating factor (G-CSF) support were maintained. Results Our study observed a 28-day survival rate of 25%, which was lower than that reported in previous literature. The median number of transfusions was 3, with an average eight-day duration post-infection diagnosis, and no side effects were observed. Conclusion While some patients benefited from GTX, overall survival rates remained modest, indicating the need for further research. Prospective, well-powered randomized controlled trials are essential to address patient selection, dosing, and duration to determine the clinical utility of GTX. This study underscores the complexity of GTX in real-world clinical practice and provides insight into the ongoing debate regarding its efficacy in treating severe neutropenic infections.

Results of Levofloxacin Prophylaxis Timing in Autologous and Allogeneic Stem Cell Transplantation: A Retrospective Cohort Study.

Background Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing hematopoietic stem cell transplantation (HSCT). Levofloxacin prophylaxis is commonly used, but the optimal timing for initiation is debated. This study aims to assess infection outcomes based on timing of levofloxacin prophylaxis (initiation at the first day of conditioning vs. after infusion of stem cells) in autologous and allogeneic HSCT patients. Methods We compared infectious episodes, responsible pathogens, and clinical outcomes based on the implementation of levofloxacin prophylaxis in patients receiving autologous or allogeneic HSCT procedures. This retrospective single-center study involved a review of the medical records of autologous and allogeneic HSCT patients treated at our adult stem cell transplantation unit between 2018 and 2020. The study included 23 patients who underwent autologous HSCT and 12 patients who underwent allogeneic HSCT. We compared the demographic data, febrile neutropenia, proven bacterial infections, and 30-day survival among the autologous and allogeneic transplant groups, including those who received oral levofloxacin 500 mg/day prophylaxis. Results Positive blood cultures (26.1% vs. 75%; p = 0.011), mean neutrophil engraftment (10.6±1.2 vs. 14.8±1.3; p<0.001), and mean platelet engraftment (11.2±1.1 vs. 15.4±3.2; p = 0.004) were all lower in autologous transplant patients versus their allogeneic counterparts. When each type of HSCT was evaluated within the same type, there were no observed differences in infection frequency, infection type, or 30-day mortality between the patient groups with different levofloxacin initiation times. Conclusion Healthcare professionals should choose the most appropriate timing for initiating levofloxacin prophylaxis based on individual patient factors and clinical circumstances while considering the cost-effectiveness implications. Further research with a larger sample size and prospective design is needed to support our findings.