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Abstract Background Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder characterized by multiple hyperproliferative polyps of the gastrointestinal tract, particularly of the colon, rectum, and stomach. SMAD4 mutations are frequently associated with multiple polyposis of the stomach; the condition causes severe bleeding and hypoproteinemia, which may progress to severe dysplasia and adenocarcinoma formation. We report our experience with the first case of total gastrectomy with pancreaticoduodenectomy following two partial jejunectomies for JPS, who presented with refractory anemia and protein-losing gastroenteropathy due to polyposis of the stomach and duodenum. Case presentation A 33-year-old Japanese man presented with the chief complaint of shortness of breath on exertion. His family history included gastric polyposis (mother, aunt, and cousin) and cerebral infarction (grandmother). Blood testing at the initial visit indicated iron-deficiency anemia, whereas endoscopy revealed multiple polyps in the duodenum and jejunum. Genetic testing revealed a 4 bp deletion (TGAA) in exon 5 of the SMAD4 gene; two partial small bowel resections were performed, but polyps grew in the remaining stomach, duodenum, and small intestine. The patient developed hypoalbuminemia and anemia, and required central venous nutrition and blood transfusion. However, because the hyponutrition and anemia remained poorly controlled, a total gastrectomy with concomitant pancreaticoduodenectomy was performed. Malnutrition and anemia improved, and there was no polyp recurrence in the remaining intestinal tract at 18 months after the surgery. Conclusions We report a case of JPS with refractory anemia and protein-losing gastroenteropathy that was treated with total gastrectomy with concomitant pancreaticoduodenectomy. Although the surgery was highly invasive, the patient’s nutritional status and anemia improved postoperatively, and the treatment was successful. However, to determine the appropriate surgical procedure, a detailed examination of the gastrointestinal lesions and the effects of the surgical invasion on nutritional status must be undertaken.

Background: Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder characterized by multiple hyperproliferative polyps of the gastrointestinal tract, particularly of the colon, rectum, and stomach. SMAD4 mutations are frequently associated with multiple polyposis of the stomach; the condition causes severe bleeding and hypoproteinemia, which may progress to severe dysplasia and adenocarcinoma formation. We report our experience with the first case of total gastrectomy with pancreaticoduodenectomy following two partial jejunectomies for JPS, who presented with refractory anemia and protein-losing gastroenteropathy due to polyposis of the stomach and duodenum. Case presentation: A 33-year-old Japanese man presented with the chief complaint of shortness of breath on exertion. His family history included gastric polyposis (mother, aunt, and cousin) and cerebral infarction (grandmother). Blood testing at the initial visit indicated iron-deficiency anemia, whereas endoscopy revealed multiple polyps in the duodenum and jejunum. Genetic testing revealed a 4 bp deletion (TGAA) in exon 5 of the SMAD4 gene; two partial small bowel resections were performed, but polyps grew in the remaining stomach, duodenum, and small intestine. The patient developed hypoalbuminemia and anemia, and required central venous nutrition and blood transfusion. However, because the hyponutrition and anemia remained poorly controlled, a total gastrectomy with concomitant pancreaticoduodenectomy was performed. Malnutrition and anemia improved, and there was no polyp recurrence in the remaining intestinal tract at 18 months after the surgery. Conclusions: We report a case of JPS with refractory anemia and protein-losing gastroenteropathy that was treated with total gastrectomy with concomitant pancreaticoduodenectomy. Although the surgery was highly invasive, the patient's nutritional status and anemia improved postoperatively, and the treatment was successful. However, to determine the appropriate surgical procedure, a detailed examination of the gastrointestinal lesions and the effects of the surgical invasion on nutritional status must be undertaken. [ABSTRACT FROM AUTHOR]

Introduction: Celiac disease (CD) is a systemic autoimmune enteropathy triggered by dietary gluten in genetically susceptible individuals. Celiac disease affects 0.6-1.0% of the population worldwide. The prevalence of CD in Pakistan is yet unknown due to under diagnosis and lack of awareness. Objective: To determine a vast variety of presenting features in subtypes of CD to overcome the burden of disease. Materials and methods: This was a prospective, comparative, cross-sectional study conducted at Gastroenterology department of Jinnah Postgraduate Medical Center, Karachi from December 2022 till June 2023. This study included all adult patients ≥18 years diagnosed with CD on the basis of clinical presentation, positive IgA and IgG anti-transglutaminase antibodies (value >12 IU/mL detected by ELISA followed by small intestinal biopsy classified as per Marsh criteria. The data obtained were analyzed on the statistical software SPSS version 23. Descriptive statistics were obtained by frequencies and percentages. Results: About 142 patients were enrolled in the study, 103 (91.5%) had classical CD (CCD) whereas 36 (25%) had non-classical (NCCD). About 89 (62.7%) were females and 53 (37.3%) were males. The mean age was found to be 23 ± 6 years. Nutritional deficiencies including anemia, B12, folate, osteopenia and low body mass index (BMI) <18 was found more in CCD group as compared with NCCD group with significant p-values. Titers of anti-TTG between CCD and NCCD were not statistically significant. Hypothyroidism and PCOS were the most common associated conditions observed in adult CD patients. Conclusion: In conclusion, CD in adults and has diverse presentations. Adults with unexplained extra-intestinal symptoms like anemia and bone pain should be investigated for CD. [ABSTRACT FROM AUTHOR]

Introduction: Iron deficiency and anemia are common after bariatric surgery. Women have a higher risk of developing such long-term complications. Though oral supplementation is indicated, intravenous iron therapy is required in some cases. Methods: This retrospective study included patients who underwent bariatric surgery between 2012 and 2018. Postoperative anemia patients receiving parental iron therapy were assessed during the first 24 months. Their baseline characteristics, surgery type, and laboratory test results were analyzed. A follow-up analysis included a subgroup of women with and without gynecological disorders. Patients with vitamin B12 or folic acid deficiencies were excluded. Results: Six hundred eleven (63.3%) met the inclusion criteria: 525 underwent gastric bypass, of which 79.6% were women. Overall, postoperative anemia was 28.9% (24.5% related to gastric bypass), especially among women (84%). Anemia refractory to oral iron therapy was observed in 12.9% of patients. All the patients requiring iron infusions (n = 54) were women, and half of them (51.8%) reported abnormal uterine bleeding. Postsurgical hemogram values were significantly lower in patients with abnormal uterine bleeding (despite the same number of infusions) than in those without gynecological disorders; 89.2% of these women had preoperative anemia. Conclusion: Anemia is frequent in bariatric surgery patients despite supplementation. Women undergoing gastric bypass with a history of gynecological disorders are prone to require more iron infusions. Consulting with the patient about a higher risk is important, and probably knowing the plan or including the opinion of an OBGYN to determine as a team the assessment, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the reduction of red blood cell transfusion (RBCT) rate in transfusion-dependent RA patients. Methods: This was a prospective quasi-randomized study, wherein patients were randomly assigned into three groups: (A) ESAs alone, (B) ferric gluconate (FG) and ESAs, and (C) FCM and ESAs. Hemoglobin and ferritin levels, as well as the number of RBCTs at 4 and 28 weeks were compared. Economic evaluation was also performed. Results: A total of 113 RA patients were enrolled. In total, 43 were treated with intravenous FG and ESAs, 38 with FCM and ESAs, and 32 with ESAs alone. At both follow-ups, erythropoietic response was increased in those receiving iron as compared with those with ESAs alone (p = 0.001), regardless of the type of iron. At one month, ferritin levels were higher in the FCM and ESA groups (p = 0.001). RBCTs were lower in both iron groups. The less costly treatment strategy was FCM, followed by FG, and lastly ESAs. Conclusions: Addition of iron to ESAs in RA reduced RBCT requirement and improved hemoglobin values. [ABSTRACT FROM AUTHOR]

Gastric antral vascular ectasia (GAVE) is an uncommon clinical entity leading to recurrent gastrointestinal bleeding. There is no consensus regarding treatment of GAVE. Endoscopic therapy is the preferred treatment option, but has a fairly high recurrence rate. Surgical resection can completely resolve GAVE, but is invasive with a relatively high risk of postoperative complications. Recently, the role of pharmacotherapy for GAVE has been recognized. However, the evidence is limited to scattered case reports or small case series. This review comprehensively summarizes the efficacy and side effects of drugs commonly used for the treatment of GAVE, including octreotide, cyproheptadine, cyclophosphamide, prednisolone, estrogen-progesterone, thalidomide, bevacizumab, and tranexamic acid. [ABSTRACT FROM AUTHOR]

Objective: Primary hyperparathyroidism (PHPT) has varied clinical presentations. Hematologic abnormalities secondary to PHPT have been described before. However, pancytopenia as the initial presentation has rarely been reported. We report a patient with PHPT who presented for evaluation of pancytopenia. Methods: Histopathology of the bone marrow at presentation is described. Bone biochemistry results and the hematologic profile before and after curative parathyroidectomy are presented. Results: A 48-year-old woman presented with pancytopenia (hemoglobin, 6.3 g/dL; total leucocyte count, 3000 cells/mm3; and platelet count, 60 000 cells/mm3), and her bone marrow study showed marrow fibrosis. Biochemical evaluation revealed hypercalcemia (15.5 mg/dL), hypophosphatemia (2.2 mg/dL), and elevated total alkaline phosphatase (4132 U/L). Bone mineral density assessment by dual-energy X-ray absorptiometry scan revealed osteoporosis at all 3 sites, which was more severe in the distal one third of the forearm. Further investigations confirmed the diagnosis of PHPT (serum parathyroid hormone, 2082 pg/mL). Following curative parathyroidectomy, in addition to normalization of calcium, there was restoration of all 3 hematologic cell lines at 3 months. Conclusion: Pancytopenia may be a rare manifestation of PHPT. Thus, it may be prudent to evaluate the calcium profile in patients with chronic refractory anemia and pancytopenia.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinicaltrials.gov using the terms "selinexor", "belantamab", "belamaf", and "multiple myeloma" without applying any limitations based on the date of the study, language, or country of origin. The most common hematological toxicity associated with these two drugs is thrombocytopenia. Cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia are the major toxicities of Sel. Keratopathy and anemia are the major toxicities of belamaf. Treatment modifications and dose interruption are usually needed when side effects are more than grade II. As these are newer drugs with limited data, continuous surveillance and monitoring are warranted during the treatment course with early mitigation strategies. [ABSTRACT FROM AUTHOR]

Background: Falciparum malaria is a common disease in our area. Apart from its classical presentation, at times it may present with refractory anemia or pancytopenia. The aim of this study was to determine the refractory anemia and pancytopenia as complications of falciparum malaria and apart from peripheral blood smears the significance of rapid antigen tests and bone marrow examination in the diagnosis of falciparum malaria. Material & Methods: The descriptive study included 200 consecutive cases of fever and refractory anemia or pancytopenia from 2011 to 2014. Stratification of patients according to the clinical scenario included Group-A having fever with refractory anemia and Group-B with fever and pancytopenia. A detailed history, thorough clinical examination, and pertinent laboratory tests were performed. All patients were treated with antimalarial drugs and followed-up for eight weeks. The pre and post treatment hematologic parameters were compared. Results: Among the 200 patients, 85 were males and 115 females. The age ranged from 15 to 55 years. Stratification of patients on clinical scenario revealed 175(87.5%) patients with fever and refractory anemia (Group-A). Among these, 125(62.5%) patients were reported smear positive for P. falciparum. In the remaining 50 smear negative patients rapid antigen tests were performed and all were reported positive. In 25 patients of Group B with fever and pancytopenia, the peripheral smear for malaria was positive only in 5 patients. In the remaining 20 cases both the peripheral blood smears and rapid antigen tests were reported negative. Bone marrow examination was planned to confirm the bone marrow suppression as the cause of peripheral pancytopenia, to exclude leukemia and to identify P. falciparum. The bone marrow examination revealed P. falciparum in all these cases. All the patients had a dramatic response to treatment with antimalarials in terms of disappearance of fever and correction of anemia and bone marrow rescue with reversal of pancytopenia to normal counts. Conclusion: Plasmodium falciparum should be considered in all cases of prolonged fever with refractory anemia or pancytopenia in malaria endemic areas, even with negative smear and rapid antigen tests. Bone examination is mandatory for the diagnosis in such cases. There is dramatic response of such patients to treatment with antimalarial drugs and hematinics.

Anemia is a global health problem affecting one-third of the world population, and half of the cases are due to iron deficiency (ID). Iron deficiency anemia (IDA) is the leading cause of disability in several countries. Although multiple mechanisms may coexist, ID and IDA causes can be classified as i) insufficient iron intake for the body requirement, ii) reduced absorption, and iii) blood losses. Oral iron represents the mainstay of IDA treatment. IDA is defined as "refractory" when the hematologic response after 4 to 6 weeks of treatment with oral iron (an increase of >=1 g/dL of Hb) is absent. The cause of iron-refractory anemia is usually acquired and frequently related to gastrointestinal pathologies, although a rare genetic form called iron-refractory iron deficiency anemia (IRIDA) exists. In some pathological circumstances, either genetic or acquired, hepcidin increases, limiting the absorption in the gut, remobilization, and recycling of iron, thereby reducing iron plasma levels. Indeed, conditions with high hepcidin levels are often underrecognized as iron refractory, leading to inappropriate and unsuccessful treatments. This review provides an overview of the iron refractory anemia underlying conditions, from gastrointestinal pathologies to hepcidin dysregulation and iatrogenic or provoked conditions, and the specific diagnostic and treatment approach. [ABSTRACT FROM AUTHOR]

Objective: To study the presentations of afebrile malaria with respect to febrile malaria. Study Design: Cross sectional descriptive. Place and Duration of Study: Combined Military Hospital (CMH) Mangla Cantt, from Jan 2015 to Jan 2017. Material and Methods: A retrospective cross sectional descriptive study was conducted on patients received at CMH Mangla during the study period. Permission from the ethical committee of hospital was obtained for the study. Malaria was diagnosed by exam of peripheral blood film slide on Leishman,s stain. Typing of the parasite was done using ICT immunochromatographic strip test. All consecutively advised malarial parasite (MP) tests on febrile and afebrile patients were included in the study. All repeated MP test on the same patients were excluded from the study. No co-incidental/asymptomatic case was diagnosed or included in the study. Results: A total of 5372 MP tests of patients were advised out of which total 1120 cases were reported positive for malaria infection during above study period. A total of 205 cases of suspected afebrile malarial patients were advised MP test. Out of which 116 cases of afebrile malaria were confirmed at Lab. The percentage ratio of total positive MP test was 21%. The ratio of positive febrile to afebrile total MP positive cases was 10:1. Among 116 afebrile patients the presentations were refractory anemia in 42 cases, elevated ALT in 35 cases, thrombocytopenia in 3 cases, & jaundice in 8 cases. All presentations of afebrile malarial patients were normalized after antimalarial treatment. Data were analyzed in excel. Descriptive statistics was applied on qualitative variables. Frequency and percentage documented. Conclusion: Malaria without fever is a statistically significant cause of morbidity among patients. Although simple to diagnose and easy to treat, omission of lab diagnosis leads to accumulation of untreated cases of afebrile malaria who are advised expensive and time wasting investigations burdening the Medicare system. Keywords: Afebrile, Alanine aminotransferase, Malaria, Refractory anemia, Thrombocytopenia

Refractory anaemia (RA) among myelodysplastic syndrome (MDS) is associated with a partial functional iron deficit and may require transfusions. In low-risk lymphoma and solid tumour patients, iron support improves erythropoietin (EPO) cost-effectiveness in treating anaemia. The aim of this study is to see if oral sucrosomial iron support improves the cost-effectiveness of EPO treatment in MDS patients affected by low-risk RA. We treated patients with EPO only or with EPO plus oral sucrosomial iron or intravenous (i.v.) iron. The need for transfusions was lowest in the group taking oral iron (p = 0.016) or not receiving supplementation at all (p = 0.022). We compared costs of EPO with i.v. ferric gluconate or oral sucrosomial iron supplementation or no iron supplementation. The oral iron group had fewer side effects, fewer patient medical visits in the out-patient setting, and fewer transfusions; this led to higher savings on direct hospital costs and indirect patient costs (lost days at work) and translated into a 50% abatement of overall expenditures. EPO treatment-related expenditures in MDS-RA patients were lowest with oral sucrosomial iron supplementation (Sideral®), with a longer interval between EPO administration in maintenance treatment, quicker hemoglobin recovery, lower ferritin increase and fewer blood transfusions. [ABSTRACT FROM AUTHOR]

Introduction: Iron-deficiency anemia is a prevalent hematological condition in children, characterized by low hemoglobin levels often caused by inadequate iron intake or blood loss. However, there are cases where anemia persists despite adequate iron therapy, being classified as iron-refractory feriprival anemia. The objective of this case report is to highlight the crucial role of a rigorous diagnostic approach in the management of refractory iron-deficiency anemia in children, focusing on identifying the underlying cause. Case Report: We present the case of a 10-year-old boy diagnosed with autism spectrum disorder and iron deficiency anemia for approximately 2 years, who underwent oral iron therapy without any improvement. The patient presents with severe normochromic, normocytic anemia, elevated ferritin levels, as well as increased inflammatory markers (ESR, C-reactive protein). Suspicion of malabsorption arises, as the patient was tested negative for Helicobacter pylori infection and celiac disease, but elevated calprotectin levels were discovered. Subsequent findings raise suspicion of an inflammatory bowel disease. Also, antinuclear antibodies (ANA) were tested and found to be at the upper limit of normal. Following this, the patient was scheduled for a colonoscopy; however, prior to the procedure, a test for Clostridium difficile was conducted, yielding a positive result. Discussions : These findings led to the suspicion of an inflammatory bowel disease, potentially underlying the refractory iron-deficiency anemia in this patient. The importance of a meticulous diagnostic approach is highlighted, focusing on identifying the underlying cause to ensure appropriate management and prevent potential complications. Conclusions: This case exemplifies the critical role of meticulous diagnostic investigations in elucidating the complex etiology of refractory iron-deficiency anemia in pediatric patients. Despite initial therapeutic efforts targeting iron deficiency, the persistent anemia prompted a comprehensive diagnostic workup, revealing potential underlying factors such as malabsorption and inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Falciparum malaria is not an uncommon infection in population of Khyber Pakhtunkhwa, Pakistan. Apart from its classical presentation, it may present with refractory anemia or pancytopenia. The objective of this study was to determine frequency of refractory anemia and pancytopenia as presentations of falciparum malaria in population of Khyber Pakhtunkhwa, Pakistan. Material & Methods: This descriptive study was conducted at the Department of Medicine, Khyber Teaching Hospital, Peshawar, Pakistan, over the years 2011 to 2014. A detailed history, clinical examination, and pertinent laboratory tests were performed for a sample of 200 cases of falciparum malaria. All patients were treated with antimalarial drugs and followed-up for eight weeks. Results: Out of 200 patients with falciparum malaria, 85 (42.5%) were males and 115 (57.5%) females. The age ranged from 15 to 55 years. Out of these 200 patients, frequency of refractory anemia was 175 (87.5%) and frequency of pancytopenia was 25 (12.5%). Among 175 cases, 125 (71.43%) were smear positive for P. falciparum and 50 (28.57%) were positive on rapid antigen tests (RATs). In 25 (12.5%) patients with pancytopenia, the smear for malaria and RATs were positive only in 5 (20%) patients. In remaining 20 (80%) cases, bone marrow examination revealed P. falciparum in all cases. All patients dramatically responded to treatment with antimalarials and supportive care including hematinics. Conclusion: Plasmodium falciparum should be considered in cases of prolonged fever with refractory anemia or pancytopenia in the malaria endemic areas, even with negative smear and rapid antigen tests. Bone marrow examination is mandatory for diagnosis in such cases. [ABSTRACT FROM AUTHOR]

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Background Myelodysplastic syndrome (MDS) is characterized by peripheral blood cytopenias, with most patients developing significant anemia and dependence on red blood cell (RBC) transfusion. In paroxysmal nocturnal hemoglobinuria (PNH), mutations in the PIGA gene lead to lack of cell-surface glycosylphosphatidylinositol, allowing complement-mediated lysis to occur. Paroxysmal nocturnal hemoglobinuria results in direct antiglobulin test--negative hemolysis and cytopenias, and up to 50% of patients with mds test positive for PNH cells. We wanted to determine whether PNH is considered to be a contributor to anemia in MDS. Methods Patients with a diagnosis of mds confirmed by bone-marrow biopsy since 2009 were reviewed. Highresolution PNH testing by flow cytometry examined flaer (fluorescein-labeled proaerolysin) binding and expression of CD14, CD15, CD24, CD45, CD59, CD64, and CD235 on neutrophils, monocytes, and RBCS. Results In 152 patients with MDS diagnosed in 2009 or later, the MDS diagnosis included subtypes associated with PNH positivity (refractory anemia, n = 7, and hypoplastic MDS, n = 4). Of 11 patients who underwent pnh testing, 1 was positive (9.0%). Reasons for PNH testing were anemia (n = 3), new MDS diagnosis (n = 2), hypoplastic MDS (n = 2), decreased haptoglobin (n = 1), increased RBC transfusion requirement (n = 1), and unexplained iron deficiency (n = 1). Conclusions Testing for PNH was infrequent in MDS patients, and the criteria for testing were heterogeneous. Clinical indicators prompted PNH testing in 6 of 11 patients. Given that effective treatment is now available for PNH and that patients with PNH-positive MDS can respond to immunosuppressive therapy, PNH testing in MDS should be considered. Prospective analyses to clarify the clinical significance of PNH positivity in MDS are warranted. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the characteristics and composition of intestinal microbiota in children with refractory epilepsy after ketogenic diet (KD) therapy and to explore the bacterial biomarkers related to clinical efficacy. Methods We prospectively analyzed 20 patients (14 males, 6 females) treated with KD. Clinical efficacy, electroencephalogram (EEG) changes, and laboratory tests were evaluated, and fecal specimens were obtained prior to and 6 months after therapy. The composition of gut microbiota was analyzed by 16S rDNA sequencing, and we screened the possible flora associated with efficacy of the KD. Results After 6 months of treatment, 2 patients were seizure free, 3 had ≥ 90% seizure reduction, 5 had a reduction of 50–89%, and 10 had < 50% reduction. All 10 responders showed an improvement in EEG. Compared with baseline, fecal microbial profiles showed lower alpha diversity after KD therapy and revealed significantly decreased abundance of Firmicutes and increased levels of Bacteroidetes . We also observed that Clostridiales, Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes were enriched in the non-responsive group. Conclusions The results show that the KD can reduce the species richness and diversity of intestinal microbiota. The changes of gut microbiota may be associated with different efficacy after KD, and specific gut microbiota may serve as an efficacy biomarker and a potential therapeutic target in patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Summary: Effectiveness and side‐effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug‐related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54‐month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow‐up visit. A total of 126 patients, with 3275 patient‐months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first‐line treatment (93%) and in combination therapy (70%). Thirty‐nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment‐limiting side effects. Drugs had similar side‐effect incidence (P = 0.363) and their side‐effect profile met those reported in the literature. Twenty‐seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. [ABSTRACT FROM AUTHOR]

Background: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD.Study Design and Methods: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS).Results: In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed.Conclusion: Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment. [ABSTRACT FROM AUTHOR]

Background: Inotuzumab ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, demonstrated superior clinical activity versus standard-of-care (SOC) chemotherapies for relapsed/refractory B-cell acute lymphoblastic leukemia in the phase 3 randomized controlled INO-VATE trial. The authors assessed patient-reported outcomes (PROs) from that study.Methods: Patients were randomized to receive either InO (1.8 mg/m2 per cycle for ≤6 cycles) or SOC (fludarabine/cytarabine [ara-C]/granulocyte colony-stimulating factor, or ara-C plus mitoxantrone, or high-dose ara-C for ≤4 cycles) and completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the EuroQoL 5 Dimensions Questionnaires at baseline, on day 1 of each cycle, and at the end of treatment. Treatment differences in PROs were assessed using longitudinal mixed-effects models with random intercepts and slopes.Results: Questionnaire completion rates in the InO (n = 164) and SOC (n = 162) arms were 85% and 65%, respectively. Baseline scores were similar between arms. Patients who received InO reported better quality of life (QoL), functioning, and symptom scores (except for constipation and emotional functioning). Least-squares mean (95% confidence interval [CI]) differences in physical, role, and social functioning and in appetite loss were significant (6.9 [95% CI, 1.4-12.3], 11.4 [95% CI, 3.2-19.5], 8.4 [95% CI, 0.7-16.1], and -8.7 [95% CI, -16.0 to -1.4], respectively; all P < .05) and had exceeded the minimally important difference of 5. Mean treatment differences in favor of InO on the EuroQoL visual analog scale and the global health status/QoL, dyspnea, and fatigue scales reached or approached the minimally important difference of 5, although without statistical significance. No dimensions were significantly worse with InO versus SOC.Conclusions: The current PRO data support the favorable benefit/risk ratio of InO for the treatment of relapsed/refractory acute lymphoblastic leukemia, with superior clinical efficacy and better QoL. Cancer 2018;124:2151-60. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated. The complete remission (CR) rate was higher in the CART19 group than that in the chemotherapy group (90.9 vs 37.9%, P = 0.000). For patients relapsed after allo-HSCT and chemotherapy, CR rates were 100% (8/8) vs 48.0% (12/25) (P = 0.009) and 85.7% (12/14) vs 31.7% (13/41) (P = 0.000), respectively. Moreover, a higher percentage in the CART19 group had results below the threshold for minimal residual disease (100 vs 7.58%, P = 0.000). In survival analysis, the overall survival rate at 12 months was higher in the CART19 group than that in the chemotherapy group (60.9 vs 10.1%, P = 0.000). For post-transplant patients achieving CR, 25.0% (2/8) and 75.0% (9/12) complicated with GVHD (P = 0.04) in the CART19 group and chemotherapy group, respectively. For all CR patients, the median duration of absolute neutrophil count less than 500/μL and platelet count less than 20,000/μL were longer in the CART19 group than in the chemotherapy group (p = 0.0047 and 0.0003, respectively). Our data demonstrated that patients with CART19s therapy acquired higher rates of remission and longer survival, confirming the encouraging application of CART19 therapy in R/R ALL. [ABSTRACT FROM AUTHOR]

The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m2 was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = .50). In both arms, more than half of patients who had received only one prior line of therapy achieved remission. The median event-free survival for CIA and FIA was 2.0 and 1.9 months (p = .48), and the median overall survival was 6.3 and 4.7 months, respectively (p = .28). No significant differences in adverse events or early mortality rates were observed. Overall, CIA and FIA resulted in similar response rates and survival in patients with relapsed/refractory AML. [ABSTRACT FROM AUTHOR]

Objective: To study the presentations of afebrile malaria with respect to febrile malaria. Study Design: Cross sectional descriptive. Place and Duration of Study: Combined Military Hospital (CMH) Mangla Cantt, from Jan 2015 to Jan 2017. Material and Methods: A retrospective cross sectional descriptive study was conducted on patients received at CMH Mangla during the study period. Permission from the ethical committee of hospital was obtained for the study. Malaria was diagnosed by exam of peripheral blood film slide on Leishman's stain. Typing of the parasite was done using ICT immunochromatographic strip test. All consecutively advised malarial parasite (MP) tests on febrile and afebrile patients were included in the study. All repeated MP test on the same patients were excluded from the study. No co-incidental/asymptomatic case was diagnosed or included in the study. Results: A total of 5372 MP tests of patients were advised out of which total 1120 cases were reported positive for malaria infection during above study period. A total of 205 cases of suspected afebrile malarial patients were advised MP test. Out of which 116 cases of afebrile malaria were confirmed at Lab. The percentage ratio of total positive MP test was 21%. The ratio of positive febrile to afebrile total MP positive cases was 10:1. Among 116 afebrile patients the presentations were refractory anemia in 42 cases, elevated ALT in 35 cases, thrombocytopenia in 3 cases, & jaundice in 8 cases. All presentations of afebrile malarial patients were normalized after antimalarial treatment. Data were analyzed in excel. Descriptive statistics was applied on qualitative variables. Frequency and percentage documented. Conclusion: Malaria without fever is a statistically significant cause of morbidity among patients. Although simple to diagnose and easy to treat, omission of lab diagnosis leads to accumulation of untreated cases of afebrile malaria who are advised expensive and time wasting investigations burdening the Medicare system. [ABSTRACT FROM AUTHOR]

Studies showed red cell distribution width (RDW) can improve the detection of morphological changes in red blood cells and the understanding of their contribution to dyserythropoiesis in myelodysplastic syndrome (MDS). The purpose of the study was to evaluate dyserythropoiesis in MDS by RDW analysis and to explore the utility of RDW in clinical practice. We retrospectively analyzed laboratory and clinical data of 101 patients (59 patients was refractory anemia (RA) according to the French-American-British (FAB) classification). In patients with RA, RDW was showed weak inverse correlation with both hemoglobin concentration (Hb) ( r s  = −0.37, P  = 0.0035) and mean corpuscular hemoglobin concentration (MCHC) ( r s  = −0.36, P  = 0.0047). On the other hand, RDW was showed weak correlation with the number of ringed sideroblasts in bone marrow ( r s  = 0.31, P  = 0.023). The increased RDW (≥15.0%) was associated with shorter overall survival (OS) ( P  = 0.0086). In patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t), effect of RDW on OS was less evident. These results suggested that increased RDW might reflect dyserythropoiesis, associated with deregulated hemoglobin synthesis and iron metabolism in MDS. Furthermore, increased RDW may have potential to be a prognostic significance in RA. [ABSTRACT FROM AUTHOR]