Case Report: Autoimmune Hemolysis Anemia After Dihydroartemisinin and Piperaquine for Uncomplicated Plasmodium falciparum Malaria

Malaria is still an endemic disease in Africa, with many imported cases in Europe. The standard treatment is intravenous artesunate for severe malaria and oral artemisinin-based combination therapy (ACT) for uncomplicated malaria. Delayed hemolytic anemia (DHA) after intravenous artesunate has been extensively described, and guidelines recommend biological monitoring until 1 month after the end of the treatment. A link with an autoimmune process is still unsure. Nevertheless, cases with positive direct antiglobulin test (DAT) have been reported. Conversely, DHA is not recognized as an adverse effect of oral ACT. Previously, only few cases of DHA occurring after oral ACT without intravenous artesunate administration have been reported. We report the case of a 42-year-old man returning from Togo. He was treated with dihydroartemisinin/piperaquine combination for uncomplicated Plasmodium falciparum malaria, with low parasitemia. Nine days after the end of the treatment, the patient developed hemolytic anemia with positive DAT. Eventually, the patient recovered after corticotherapy. After excluding common causes of autoimmune hemolytic anemia, we considered that dihydroartemisinin/piperaquine treatment was involved in this side effect.

Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice

Lung emphysema and chronic bronchitis are the two most common causes of chronic obstructive pulmonary disease. Excess macrophage elastase MMP-12, which is predominantly secreted from alveolar macrophages, is known to mediate the development of lung injury and emphysema. Here, we discovered the endolysosomal cation channel mucolipin 3 (TRPML3) as a regulator of MMP-12 reuptake from broncho-alveolar fluid, driving in two independently generated Trpml3−/− mouse models enlarged lung injury, which is further exacerbated after elastase or tobacco smoke treatment. Mechanistically, using a Trpml3IRES-Cre/eR26-τGFP reporter mouse model, transcriptomics, and endolysosomal patch-clamp experiments, we show that in the lung TRPML3 is almost exclusively expressed in alveolar macrophages, where its loss leads to defects in early endosomal trafficking and endocytosis of MMP-12. Our findings suggest that TRPML3 represents a key regulator of MMP-12 clearance by alveolar macrophages and may serve as therapeutic target for emphysema and chronic obstructive pulmonary disease.

Medication Errors in Pediatrics: Proposals to Improve the Quality and Safety of Care Through Clinical Risk Management

Medication errors represent one of the most common causes of adverse events in pediatrics and are widely reported in the literature. Despite the awareness that children are at increased risk for medication errors, little is known about the real incidence of the phenomenon. Most studies have focused on prescription, although medication errors also include transcription, dispensing, dosage, administration, and certification errors. Known risk factors for therapeutic errors include parenteral infusions, oral fluid administration, and tablet splitting, as well as the off-label use of drugs with dosages taken from adult literature. Emergency Departments and Intensive Care Units constitute the care areas mainly affected by the phenomenon in the hospital setting. The present paper aims to identify the risk profiles in pediatric therapy to outline adequate preventive strategies. Precisely, through the analysis of the available evidence, solutions such as standardization of recommended doses for children, electronic prescribing, targeted training of healthcare professionals, and implementation of reporting systems will be indicated for the prevention of medication errors.

Pattern of referral of sick Omani pilgrims from Omani medical mission during hajj 2019 (Preprint)

BACKGROUND Annually, in the month of Dhul hijjah, over 2 million Muslims travel to Saudi Arabia to perform Hajj. Hajj is the biggest mass gathering globally, which creates a significant influence on Hajjes' health. The Omani medical mission is the official delegation from the Omani government to Saudi Arabia to serve the Omani hajjees regarding their health issues. OBJECTIVE This study investigates the referral rate and pattern of diseases among hajjees referred by the Omani medical mission during Hajj 1440 H. METHODS We conducted a cross-sectional study at the Omani Medical missions in Makkah, Madinah, Mina, and Arafat. Data was collected via a predesigned form. All Omani pilgrims presenting to the mission who were referred to local hospitals were included. RESULTS The total number of cases was 5000, of which 106 (2.1%) were referred to local hospitals (21.2 per 1000 hajjees). The most common causes of referral were cardiovascular diseases (23.6%), followed by gastrointestinal disease (17.9%) and trauma (16.9%). Males comprised 60.1%. Their mean age was 47.3 years (SD ±11.27), with the highest referrals in the 51-60 years age group (30%). Over half (55.7%) had co-morbidities. Patients' mean time to reach the clinic was 8.87 min (SD ±6.41), with 65% arriving in 5 min or less. The mean time needed to reach the hospital by ambulance was 11.39 min (SD ±6.6), with 36% arriving within 5 min. Of the referrals, 42% were admitted into hospital. Hospitalization was significantly higher among patients with chest pain (P-value < 0.0057), diabetics (P-value < 0.0001), and patients with Heart Disease (P-value = 0.013). CONCLUSIONS The most common causes for referral of Hajjees from the Omani Medical Mission were cardiovascular diseases, gastrointestinal disease, and trauma. This information should assist the Omani government in planning their medical services in hajj season in future years.

Progress in the Treatment of HIV-Associated Lymphoma When Combined With the Antiretroviral Therapies

With the wide use of combination antiretroviral therapy (cART), the life expectancy of HIV-infected individuals drastically improved. However, HIV infection and HIV-associated cancers were the most common causes of death in the HIV-infected populations. The HIV-associated cancers are divided into acquired immune deficiency syndrome (AIDS)-defining and non-AIDS-defining cancers based on the incidence among the HIV-infected patients. Among HIV-associated cancers, acquired immune deficiency syndrome-related lymphoma (ARL) is still the most common condition and the leading cause of HIV/AIDS-related deaths. Diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) are the most common subtypes of the ARL. Although Hodgkin’s lymphoma (HL) is not considered as an AIDS-defining cancer, incidence of HL in HIV-infected individuals is higher than the general population. The review summarizes the new progress in the treatment of HIV-associated lymphoma.

Postmortem Study of Organ-Specific Toxicity in Glioblastoma Patients Treated with a Combination of Temozolomide, Irinotecan and Bevacizumab

Purpose Systemic monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as Irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma. Most patients tolerated these regimens well with well-established sides effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ-specific toxicities have never been examined by postmortem studies. Methods Postmortem tissues (from all major organs) were prospectively collected and examined by standard institution autopsy and brain cutting procedures from 76 decedents, including gliomas (N=68, 44/M, and 24/F) and brain metastases (N=8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs and brain samples harvested. Electronic microscopic (EM) study was carried on selected subjects kidney samples per standard EM protocol. Results Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at glioma recurrence. Exposure to IRI significantly increased the frequency of CM (p=0.05). No unexpected adverse events were detected clinically or permenant end-organ damage by postmortem examination among subjects who received TIB compared to subjects who received standard of care (SOC) therapies. Among glioma decedents, the most common causes of death (COD) were tumor progression (63.2%, N=43), followed by aspiration pneumonia (48.5%, N=33). No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis. Conclusion IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. There is no permanent organ-specific toxicity among glioma decedents who received prolonged BEV, TMZ or TIB regimen based chemotherapies except expected occasional myelosuppresson. COD are most commonly resulted from glioma tumor progression and aspiration pneumonia.

Management of Appendicitis

Appendicitis is one of the most common causes of acute abdomen with life time risk between 6 and 8% and it’s a most common non obstetric surgical emergency during pregnancy. Appendicitis is claimed to be unknown in the villages of India and China in paper by A. M. Spencer. The reason is simply due to the fact that diagnostic facilities do not exist and cases are not recognized. So diagnosing acute appendicitis accurately and efficiently can reduce morbidity and mortality from perforation and other complications. Surgical intervention is the first choice for appendicitis with medical management being reserved for special situations.

Occam’s Razor and Managing Acute Thrombosis in the COVID-19 Era

The COVID-19 pandemic has profoundly influenced the practice of medicine in Australia over the last 24 months. Recently, the development of several vaccines to COVID-19 has been accompanied by reports of an associated rare syndrome of thrombosis and thrombocytopaenia (VITTS). The possibility of this rare disorder confronts all clinicians who deal with acute thrombosis, particularly given the prevalence of patients who have recently been immunised. However, VITTS remains rare, and we believe unnecessary focus on its potential diagnosis may distract from other more common causes of acute thrombosis. We discuss this with reference to a recent case at our institution.

Men’s health and osteoporosis: modern treatment and prevention options

Osteoporosis (OP) has traditionally been seen as a pathology that mainly occurs in postmenopausal women and elderly men, and until recently, the problem of this disease among males has not been given sufficient priority. At the moment, however, OP in men is widely acknowledged to be an important issue of modern health care. Given the etiological and pathogenetic characteristics, two categories of OP have been identified: primary and secondary. In the structure of male OP, the secondary category of OP accounts for up to 40-60 % of all cases. Hypogonadism is one of the common causes of bone loss in men. Initially, males develop a larger bone mass compared to women and, accordingly, greater bone strength. Men over the age of 50 do not undergo rapid bone mass loss, as women do after menopause, and the bone mass decreases more gradually, in a linear manner. With ageing, the trabecular number (Tb.N) in men are relatively maintained with underlying more pronounced thinning of Tb. N associated with decreased osteoblast-forming activity. Although the prevalence of OP among men is significantly lower than among women, the clinical consequences of OP in men are of a great importance. The primary strategy of the anti-osteoporotic therapy is to prevent OP and low-traumatic fractures. According to the current guidelines for the treatment of OP in men, bisphosphonates (BP) are the drugs of choice. Zoledronic acid is a highly effective nitrogen-containing BP, the first drug to be injected once a year. Intravenous injection of zoledronic acid is as effective in reducing the risk of fractures in men as in women.

Phage Display Preparation of Specific Polypeptides in Atherosclerotic Foam Cells

Atherosclerosis and related complications are the most common causes of death in modern societies. Macrophage-derived foam cells play critical roles in the initiation and progression of atherosclerosis. Effective, rapid, and instrument-independent detection in the early stage of chronic atherosclerosis progression could provide an opportunity for early intervention and treatment. Therefore, as a starting point, in this study, we aimed to isolate and prepare foam cell-specific polypeptides using a phage display platform. The six target polypeptides, which were acquired in this study, were evaluated by ELISA and showed strong specificity with foam cells. Streptavidin coupled quantum dots (QDs) were used as fluorescence developing agents, and images of biotin-modified polypeptides specifically binding with foam cells were clearly observed. The polypeptides obtained in this study could lay the foundation for developing a rapid detection kit for early atherosclerosis lesions and could provide new materials for research on the mechanisms of foam cell formation and the development of blocking drugs.