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The use of drugs that have been previously defined for certain indications in new indications is defined as the repurposing/repositioning of the drug. The requirement of all clinical research steps that starts from healthy volunteers, due to the slowness of new drug discovery, longer time to reach the market, and high cost to develop a new drug, make drug repurposing an attractive pharmacoeconomic solution. Repositioning of drugs becomes even more important, especially in situations where time is vital and emergency in drug development such as pandemics. In this review, we have both summarized the techniques used for drug repositioning and evaluated drugs that have been repositioned in Coronavirus Disease (COVID-19) treatment based on three main strategies, target-disease and drug-based. Considering the availability of the results of pharmacovigilance studies and long-term toxic effects of old drugs provide an important advantage compared to traditional drug discovery in COVID-19 treatment, where sepsis and multi-organ dysfunction can occur.

Background Pneumatosis cystoides intestinalis (PCI) is a disorder in which widespread air sacs are present in mucosa, submucosa, subserosa, and intraabdominal area of the intestinal wall. It has a heterogeneous clinical presentation as a rare complication of intestinal graft-versus-host disease (GVHD). Computed tomography is the preferred imaging method for the diagnosis. Since the air sacs could be ruptured spontaneously, the presence of free air in the peritoneal cavity does not confirm intestinal perforation. The conservative treatment approach is sufficient in cases that do not require urgent surgical intervention, such as perforation or obstruction. Case Here, we present a 2.5-year-old patient diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH), who underwent allogeneic hematopoietic stem cell transplantation from a matched unrelated donor (MUD) and developed PCI secondary to intestinal GVHD 14th months after HSCT. Conclusions Pneumatosis cystoides intestinalis, which is a rare complication, should be kept in mind, especially in patients with intestinal GVHD and receiving intensive immunosuppressive, octreotide, and steroid treatment after HSCT.

We aimed to evaluate the impact of pretreatment folate and vitamin B12 deficiencies on the frequency of complications and peripheral blood recovery, in children with acute lymphoblastic leukemia (ALL). Pre-induction serum folate and vitamin B12 levels of 88 newly diagnosed ALL patients were evaluated retrospectively. Folate 1.0 × 109/L and platelet count > 100 × 109/L at 33rd day of chemotherapy were also evaluated. Folate or vitamin B12 deficiencies were observed in 21 (23%) and 40 (45%) children, respectively. Peripheral blood counts, complications rates, and transfusion needs were not statistically different between deficient and normal level groups during induction. The number of febrile days, though not statistically significant, was higher in the both deficient groups. Seventeen of 40 (42.5%) patients with vitamin B12-deficient and 12 of 21 (57.1%) folate-deficient patients experienced at least one episode of FN during induction. FN was more common in folate-deficient group, but that was not statistically significant. Complete peripheral blood recovery at 33rd day of induction was seen in 40% in the vitamin B12-deficient group and 28.6% in folate-deficient group. Peripheral blood recovery rate at day 33 was also similar in both deficient and normal level groups. Although pre-induction low serum levels of vitamin B12 and folate did not have statistically significant impact on disease-/treatment-related complications and peripheral blood recovery at induction, the frequency of FN and number of febrile day were higher in both deficiencies and folate-deficient patients, respectively.

The purpose of this paper is to guide the understanding of preventive oral health measures to improve overall health in older adults. Oral health is a key indicator of overall health, well-being, and quality of life, yet, oral health status among older adults has remained alarmingly poor. Common oral conditions include dental decay, periodontal disease, tooth loss, dry mouth, and malodor. The connection between oral and systemic health has been established and this relationship is affected by various interrelated factors which pose many threats to older adults’ health. Documented factors may range from chronic diseases, use of medications, individual lifestyle, decline in cognitive and physical functioning, access to care, to several social indicators of oral health. Dental disease and poor oral health are largely preventable through healthy lifestyle behaviors and effective management of chronic systemic diseases. A collaborative team approach is necessary to ensure that older adults receive comprehensive care appropriate for their complex medical and dental needs.

Background: The neuro-ichthyotic diseases are clinically and genetically heterogeneous. The purpose of this study was to evaluate the clinical and neuroradiological findings and to analyze mutation in 15 patients with neuro-ichthyotic diseases. Materials and Methods: We retrospectively analyzed the records of 15 patients with the diagnosis of neuro-ichthyotic diseases. Results: Eight female and seven male patients (age range 11 months–52 years) were investigated. There were eight patients with Sjögren–Larsson syndrome (SLS), five patients with multiple sulfatase deficiency (MSD), one patient with Chanarin–Dorfman's syndrome, and one patient with mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia (MEDNIK) syndrome. Parental consanguinity was found in all the patients except one. All patients had ichthyosis. Diagnosis was performed with genetic study. Conclusions: Because biochemical and clinical findings are variable, the diagnosis is difficult in most of the cases. Detailed skin and physical examinations are mandatory in these patients. Genetic tests are necessary for accurate diagnosis.

Bu, combined with TDM-guided dosing, is associated with fewer graft failures/relapses and lower toxicity in pediatric HSCT. We aimed this retrospective study for comparison of weight- and age-based dosing in terms of clinical outcomes such as time to engraftment, early complications, EFS, OS, and toxicity profiles in children receiving iv Bu. Sixty-one children who underwent HSCT from April 2010 to February 2013 by means of a Bu-based conditioning regimen and completed 100 days after transplantation at Ankara Children?s Hematology and Oncology Hospital Bone Marrow Transplantation Unit were enrolled in this study. SOS and neutropenic fever occurred more frequently in the weight-based dosing group. We found a statistically significant correlation between Bu dose and the incidence of SOS (r = 0.26, p = 0.04). Multivariate analysis showed only weight-based dosing of Bu was a significant predictor of SOS (HR = 9.46; p = 0.009). However, no relationship was found between two groups in terms of hemorrhagic cystitis, engraftment syndrome, acute or chronic GvHD, time to engraftment, chimerism, TRM, OS, and EFS rates. Weight-based dosing of Bu may cause higher incidence of SOS and early infectious complications at the places where TDM of Bu cannot be performed.

Lung cancer metastasis to the pituitary gland is an unusual pathology. In this report, we present a 63-year-old woman with pituitary gland mass due to lung cancer metastasis. The patient was admitted to our hospital because of difficulty of vision. She had a lung cancer diagnosis (adenocarcinoma) and had an operation for a mass in the left lung. There was no problem with her follow-up except vision difficulty that was noted in her last examination. Cranial magnetic resonance imaging revealed a pituitary mass in her sella turcica. The magnetic resonance imaging also showed left frontal metastatic mass. Radiotherapy was performed but failed, and the mass lesion was found to have progressed. The patient died 3 months after the diagnosis of metastasis was established. This case represents a rare report in the literature. Pituitary metastases may rarely be seen in the late stages of lung cancer and are even more rare in women. Clinical characteristics generally resemble the other hormonally unfunctional pituitary masses. Radiotherapy may not be as effective as for the other cranial metastases.

Depression in the terminally ill has never been examined systematically. Frequently depression has been perceived as an inevitable part of illness. The purpose of the present study was to develop an instrument (the Mood Evaluation Questionnaire) to measure depression among terminally ill patients. The MEQ and the Geriatric Depression Scale were completed by 27 hospice patients. A Modified Karnofsky score and index of somatic complaints were obtained. There was no correlation among the Modified Karnofsky, the number of somatic complaints, and the level of depression. However the MEQ and GDS were highly correlated (p

To our knowledge, the occlusion of arteries and platelet hyperaggregation have not been reported in patients with malignant mesothelioma. However, venous thromboembolism, especially in the pulmonary vasculature in association with thrombocytosis and hyperfibrinogenemia, are commonly noticed in this disorder. Furthermore, we detected enhanced platelet aggregation in a case of malignant peritoneal mesothelioma with internal carotid artery occlusion in whom there were postsplenectomy thrombocytosis and hyperfibrinogenemia. The possible mechanisms of ICA occlusion in this patient, including the role of MPM and postsplenectomy state, thrombocytosis, platelet functional changes, and other factors were investigated and discussed.

Several prognostic factors have been described but there are few studies evaluating the prognostic importance of seizure in patients with glioblastoma multiforme (GBM).To evaluate the prognostic importance of seizure at the time of the diagnosis of glioblastoma multiforme (GBM) and compare it with other known prognostic factors.Between January 1994 and December 2000, 81 patients underwent irradiation for intracranial GBM at our institution. The criteria for inclusion in this study were biopsy-proven GBM, being treated for primary disease. Seventy-six patients were retrospectively evaluated and the remaining five patients could not be enrolled due to lack of details.The prognostic importance of age, sex, performance status, a history of seizure at diagnosis, extent of surgery, radiotherapy field and dose were studied.The Kaplan-Meier method, the Log rank test, the Cox proportional hazard model and the Mann-Whitney U test were used for statistical analysis.Survival at first and second years was 19.74% and 4.81%, respectively. Univariate analysis revealed age, performance status, history of seizure, and radiotherapy dose as significant prognostic factors and with multivariate analysis age, history of seizure and radiotherapy dose were positive prognostic factors.This study concluded that in GBM, history of seizure prior to diagnosis of GBM was a positive prognostic factor.

The normal capillary and venous hematologic values for neonates have not been defined clearly. It is well known that capillary blood has higher hemoglobin (Hb) and hematocrit (Hct) values than venous blood. In a recent study, we reported differences between capillary and venous complete blood counts (CBC) in healthy term neonates on day 1 of life. The aim of this study was to extend our previous investigation. Term neonates (n=141) were stratified into four groups by days of postnatal age: group 2 (day 7, n=38), group 3 (day 14, n=35), group 4 (day 21, n=32) and, group 5 (day 28, n=36). Data from our previous study were included in the statistical analysis as group 1 (day 1, n=95). A CBC and differential count were carried out on each capillary and venous sample drawn simultaneously. Within each group, the mean and standard deviation for each parameter in capillary and venous blood were calculated and then compared using the paired sample t-test. In all groups, the capillary blood samples had higher Hb, Hct, red blood cell (RBC), white blood cell (WBC), and lymphocyte counts. In each group, venous platelet counts were significantly higher than the corresponding capillary values. There was also a trend toward higher venous mean corpuscular volume, higher capillary polymorphonuclear leukocyte (PML) count and mean platelet volume in all groups. In both capillary and venous blood, Hb, Hct, RBC, MCV values and WBC, lymphocyte, PML counts decreased and platelet counts increased steadily during neonatal period. This study reveals that CBC parameters and differential counts may differ depending on the blood sampling used. The findings underline the importance of considering the sample source when using hematologic reference ranges for healthy or septic neonates. When interpreting results, the term 'peripheral blood' should be replaced with 'capillary blood' or 'venous blood' so that an accurate assessment can be made.

A 2-year-old hydrocephalic boy who had suffered multiple shunt failures was evaluated for hypercoagulability after a thrombus was removed from his right atrium. The work-up revealed that the patient had the heterozygous form of activated protein C resistance and false type 2 protein C deficiency by the clotting method. His protein C activity was normal by the chromogenic method. We suggest that patients having hydrocephalus, shunt-associated thrombus formation, or both should be evaluated for thrombophilic disorders, and protein C activity should be measured by chromogenic assay in patients with documented activated protein C resistance. ( J Child Neurol 2001; 16:862-863).

We report a neonate who presented with hypotonia, hypoglycemia, and severe lactic acidosis. The patient's acidosis did not respond to bicarbonate replacement and dialysis. Postmortem liver samples revealed portal dilatation, fibrosis, canalicular proliferation, cholestasis, and hepatocellular hemosiderosis. Vacuolization of bone marrow precursors suggested a diagnosis of Pearson syndrome. A common mitochondrial DNA deletion of 4,978 bp was found. We emphasize that Pearson syndrome should be considered in neonates with lactic acidosis despite absence of anemia.

Chronic neutropenia in childhood has many definable causes and thus a clear cause cannot be identified in a large group of patients. Since the committed stem cell is involved in this disorder, growth factors such as granulocyte colony-stimulating factor (G-CSF) may play an important role in the treatment of severely affected children. Because of the side effects and cost, the use of G-CSF should be restricted to a minimum dose. Here we report a child with chronic neutropenia in whom intermittent-low doses of G-CSF were successfully used over a long period.

Idiopathic chronic neutropenia is characterized by a variable pattern of age at the onset of neutropenia, neutrophil counts, maturational arrest at the promyelocyte/myelocyte stage in the bone marrow, and recurrent pyogenic infections without any underlying disease or drug administration. There have been reports of lack of response to conventional-dose steroid therapy, but in recent studies it has been shown that high-dose corticosteroids are effective in several neutropenic states. Here we report an apparent response to high-dose methylprednisolone in a patient with idiopathic chronic neutropenia.

A five-year-old girl was admitted to the hospital with fever and tender lymphadenopathy. She was diagnosed with acute lymphoblastic leukemia (ALL-L3). Because of infection she was given antibiotics and a blood transfusion. Her bone marrow was in remission after 15 days without chemotherapy. This case emphases the role of transfusion and/ or infection in obtaining complete remission without chemotherapy.

Hemophilic pseudotumor is one of the most serious complications of hemophilia and is usually treated with extensive surgery. A new treatment approach is radiotherapy. Patients with long-bone pseudotumors are usually treated with high doses of radiotherapy greater than 1500 cGy. We treated a 13-year-old hemophilic boy who had a pseudotumor of the tibia with low-dose radiotherapy (600 cGy). There was no complication during the two-and-a-half-year follow-up. Improvement of both the clinical and radiological status of the patient was noteworthy. We would like to suggest the use of low-dose radiotherapy in patients with hemophilic pseudotumors.

Platelet function was studied in a child with myelodysplastic syndrome (MDS: refractory anemia with an excess of blasts) and a child with acute myeloblastic leukemia (AML-M6) associated with trilineage myelodysplasia (TMDS). An acquired Bernard-Soulier-like platelet defect was considered in both patients with the findings of prolonged bleeding time and abnormally large platelets that failed to aggregate in response to ristocetin. In contrast to findings in von Willebrand's disease, the abnormal response of platelets to ristocetin could not be corrected by the addition of normal flesh plasma. The detection of abnormal platelet aggregation response to ristocetin may be a useful diagnostic finding for clonal disorders causing impaired platelet function in MDS and coexistent TMDS associated with AML. Further studies of ristocetin-induced platelet aggregation in a large number of these patients are required.

Etoposide is a semi-synthetic, topoisomerase active podophyllotoxin derivative which frequently causes deletions and rearrangements on chromosomes 11q23 and 11q22. It can cause therapy-related, acute myeloblastic leukemia in patients receiving the drug in a schedule-dependent manner. Here we present a case with acute lymphoblastic leukemia who developed secondary acute myeloblastic leukemia 28 months after the beginning of therapy which contained etoposide on an every-other-week schedule.

High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML), therefore we used HDMP in the treatment of four children with myelodysplastic syndrome (MDS). Two patients had refractory anemia with an excess of blasts in transformation (RAEB-t) with extramedullary infiltration (EMI), one had chronic myelomonocytic leukemia with pleural effusion, and one had RAEB. HDMP was administered orally at a single dose of 20-30 mg/kg/day combined with low-dose cytosine arabinoside (LD Ara-C) (10 mg/m2, 12-hourly s.c.) for 2 weeks. The treatment continued with mitoxantrone (10 mg/m2, i.v.) and Ara-C (5 mg/kg, i.v.) once a week for four doses followed by maintenance chemotherapy. All patients achieved hematologic remission 2-4 weeks after initiation of treatment. Extramedullary infiltration disappeared in all cases within 2 weeks to 3 months after initiation of therapy. With the exception of two patients who relapsed 6 and 24 months after remission, treatment could be stopped in others who remained in remission for 36 months without evidence of EMI; 6 months later one of them developed myelodysplastic relapse (RAEB). No side effects related to HDMP treatment were noted, but hyperleukocytosis developed in two patients who initially had high WBC counts. We suggest that the addition of HDMP with or without LD Ara-C to cytotoxic chemotherapy offers a promising alternative in cases not considered suitable for bone marrow transplantation.

Autoimmune hemolytic anemia may occur in the course of some viral diseases such as Coxsackie virus, cytomegalovirus, Epstein Barr virus, Influenza A, herpes simplex virus, and rarely hepatitis B virus infection. The role of being heterozygous for beta-thalassemia in hemolysis during acute viral hepatitis is not known. In this report, we present an eight-year-old boy with jaundice and anemia. The diagnosis of hepatitis B virus infection and hemolytic anemia were made on the basis of physical and laboratory findings. A hemoglobin electrophoresis revealed that the child was heterozygous for beta-thalassemia. No specific etiology could be found for hemolytic anemia. It remained unclear whether hemolytic anemia in this patient was merely a coincidental finding or whether hepatitis B virus infection and beta-thalassemia trait had played a role in causing hemolysis.

Kostmann's syndrome is a congenital disorder characterized by impairment of myeloid differentiation in bone marrow with severe absolute neutropenia. A 17-month-old girl was admitted to the hospital with complaints of recurrent skin infections since birth and severe pneumonia of the right lung which had been resistant to antibiotics since the patient was eight months old. Anemia, severe neutropenia and maturational arrest of granulocytes at the myelocyte stage in bone marrow were detected. At the age of 20 months, a right pneumonectomy was performed because of resistant cystic infection. Postoperatively, she was diagnosed with Kostmann's syndrome. Recombinant human granulocyte-colony-stimulating factor (rhG-CSF) was administered intravenously at a dose of 3 micrograms/kg/day, gradually increasing to 60 micrograms/kg/day in sequential seven-day courses to obtain a neutrophil count of more than 500 cells/mm3. Absolute neutrophil counts increased to greater than 1000 cells/mm3 at a dose of 60 micrograms/kg/day, and at that time bone marrow aspiration revealed an increase in neutrophilic granulocytic precursors beyond the myelocyte stage. In order to maintain the neutrophil response, a dose of 20 micrograms/kg/day rhG-CSF subcutaneously was continued successfully. The patient has tolerated rhG-CSF treatment without complications, and infectious attacks have significantly decreased.

A nine-month-old girl with osteomyelitis related to BCG vaccination is presented. The patient did not have any clinical evidence of immunodeficiency. Her X-ray examination showed a lytic lesion of the right tibia and of the left ulna. Histopathological examination of biopsy material revealed a chronic granulomatous inflammatory reaction. She improved with intermittent short course antituberculosis therapy.

Questionnaire measures of the narcissistic personality disorder can predict healthy and unhealthy self-functioning. That this outcome might support Heinz Kohut's psychoanalytic psychology of the self was tested in a sample of 354 undergraduates. In canonical correlations, factors from the Narcissistic Personality Inventory were associated more strongly with grandiose than with idealizing immaturities in Kohut's bipolar self, while difficulties in interpersonal relationships (i.e., poor object relations) were associated more strongly with idealizing deficits. Zero-order and partial correlational data were congruent with Kohut's hypothesis that self-grandiosity can include elements of both “pathology” and relative mental health, but canonical correlations did not support Kohut's claim that narcissism can be described in a bidimensional self-structure.

Importance: The U.S. arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals and/or persons with a prior history of infection, comprehensive data describing infections among immunologically naïve adults is lacking., Objective: To examine COVID-19 acute and post-acute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave., Design: A prospective cohort undergoing high-resolution symptom and virologic monitoring between June 2021 and September 2022., Setting: Multisite recruitment of community-dwelling adults in 8 U.S. states., Participants: Healthy, unvaccinated adults between 30 to 64 years of age without an immunological history of SARS-CoV-2 who were at high-risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 PCR testing., Exposures: Omicron (BA.1/BA.2 lineages) versus Delta SARS-CoV-2 infection, defined as a positive PCR that occurred during a period when the variant represented ≥50% of circulating SARS-CoV-2 variants in the participant's geographic region., Main Outcomes and Measures: The main outcomes examined were the prevalence and severity of acute (≤28 days post-onset) and post-acute (≥5 weeks post-onset) symptoms., Results: Among 274 immunologically naïve participants, 166 (61%) contracted SARS-CoV-2. Of these, 137 (83%) and 29 (17%) infections occurred during the Omicron- and Delta-predominant periods, respectively. Asymptomatic infections occurred among 6.7% (95% CI: 3.1%, 12.3%) of Omicron cases and 0.0% (95% CI: 0.0%, 11.9%) of Delta cases. Healthcare utilization among Omicron cases was 79% (95% CI: 43%, 92%, P =0.001) lower relative to Delta cases. Relative to Delta, Omicron infections also experienced a 56% (95% CI: 26%, 74%, P =0.004) and 79% (95% CI: 54%, 91%, P <0.001) reduction in the risk and rate of post-acute symptoms, respectively., Conclusions and Relevance: These findings suggest that among previously immunologically naïve adults, few Omicron (BA.1/BA.2) and Delta infections are asymptomatic, and relative to Delta, Omicron infections were less likely to seek healthcare and experience post-acute symptoms.