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Hypertension is the leading risk factor of mortality in Nepal accounting for â¼33 000 deaths in 2016. However, more than 50% of the hypertensive patients are unaware of their status. We participated in the May Measurement Month 2017 (MMM17) project initiated worldwide by the International Society of Hypertension to raise the awareness on the importance of blood pressure (BP) screening. In this paper, we discuss the screening results of MMM17 in Nepal. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017 following the standard MMM protocol. Data were collected from 18 screening sites in 7 districts covering 5 provinces. Screenings were conducted either in health facilities, public places, or participants' homes. Trained volunteers with health science background and female community health volunteers were mobilized to take part in the screening. A total of 5972 individuals were screened and of 5968 participants, for whom a mean of the 2nd and 3rd readings was available, 1456 (24.4%) participants had hypertension; 908 (16.8%) of those not receiving treatment were hypertensive; and 248 (45.2%) of those being treated had uncontrolled BP. MMM17 is the first nationwide BP screening campaign undertaken in Nepal. Given the suboptimal treatment and control rates identified in the study, there is a strong imperative to scale up hypertension prevention, screening, and management programmes. These results suggest that opportunistic screening can identify significant numbers with hypertension. Mobilization of existing volunteer networks and support of community stakeholders, would be necessary to improve the overall impact and sustainability of future screening programmes.
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Immune checkpoint inhibitors (ICI) such as program cell death protein 1 (PD-1) inhibitors are widely used for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal (GE) junction adenocarcinoma. Immune-related adverse events (irAE) such as endocrinopathies have been reported after patients received ICI. We report a case of pembrolizumab-induced hyperthyroidism and type 1 diabetes mellitus (DM1) presenting with diabetic ketoacidosis (DKA). A 53-year-old African American male with no history of diabetes or hyperthyroidism was treated with two cycles of pembrolizumab for recurrent GE junction adenocarcinoma after which he was admitted with hyperthyroidism (thyroid stimulating hormone [TSH] 0.070mIU/L, free thyroxine 1.85mIU/L) and DKA (pH 7.06, glucose 583 mg/dL, beta-hydroxybutyrate 8.63 mmol/L, anion gap 27 meq/L). The patient was treated with intravenous insulin and aggressively hydrated. Given the lack of other precipitating factors for the two endocrinopathies, it was determined that the most likely etiology was recent treatment with pembrolizumab (a PD-1 inhibitor). In our case, pembrolizumab monotherapy developed two irAE (hyperthyroidism and DKA), which is unique as most combined immunotherapy regimens are associated with the development of multiple endocrinopathies. Our case emphasizes the importance of baseline monitoring of thyroid function and blood glucose prior to the start of ICI to monitor and evaluate patients with immune-related adverse events, including endocrinopathies.
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Paroxysmal nocturnal hemoglobinuria (PNH) results from a mutation in the phosphatidylinositol glycan class-A gene which causes uncontrolled complement activation with resultant intravascular hemolysis and its sequelae. Eculizumab is a terminal complement inhibitor that blocks this complement activation and has revolutionized the treatment of PNH but comes with an enormous price which can have catastrophic health expenditure in low-middle income countries (LMIC) like Nepal. Here, we discuss the potential way forwards in the treatment of PNH in Nepal and other LMICs.
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Hemoglobinúria Paroxística , Humanos , Hemoglobinúria Paroxística/tratamento farmacológico , Gastos em Saúde , Nepal , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
The advent of next-generation sequencing (NGS) has allowed for the identification of novel therapeutic targets for patients with uncommon cancers. It is well known that fusion translocations are potent driver of cancer pathogenesis and can render tumors exquisitely sensitive to matching targeted therapies. Here we describe a patient with ALK-fusion positive widely metastatic salivary ductal carcinoma, who achieved a durable complete response from alectinib, a potent and specific ALK tyrosine kinase inhibitor. This case serves as another reminder that ALK-fusions can be targeted regardless of histology and can afford patients dramatic and durable benefit. It also emphasizes the need for insurance coverage for such beneficial therapies. While ALK fusions are exceedingly rare in salivary ductal carcinoma, the presence of multiple other targetable aberrations supports the recommendation for universal NGS testing for such tumors.
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Antibody-drug conjugates (ADCs) are at the forefront of the drug development revolution occurring in oncology. Formed from three main components-an antibody, a linker molecule, and a cytotoxic agent ("payload"), ADCs have the unique ability to deliver cytotoxic agents to cells expressing a specific antigen, a great leap forward from traditional chemotherapeutic approaches that cause widespread effects without specificity. A variety of payloads can be used, including most frequently microtubular inhibitors (auristatins and maytansinoids), as well as topoisomerase inhibitors and alkylating agents. Finally, linkers play a critical role in the ADCs' effect, as cleavable moieties that serve as linkers impact site-specific activation as well as bystander killing effects, an upshot that is especially important in solid tumors that often express a variety of antigens. While ADCs were initially used in hematologic malignancies, their utility has been demonstrated in multiple solid tumor malignancies, including breast, gastrointestinal, lung, cervical, ovarian, and urothelial cancers. Currently, six ADCs are FDA-approved for the treatment of solid tumors: ado-trastuzumab emtansine and trastuzumab deruxtecan, both anti-HER2; enfortumab-vedotin, targeting nectin-4; sacituzuzmab govitecan, targeting Trop2; tisotumab vedotin, targeting tissue factor; and mirvetuximab soravtansine, targeting folate receptor-alpha. Although they demonstrate utility and tolerable safety profiles, ADCs may become ineffective as tumor cells undergo evolution to avoid expressing the specific antigen being targeted. Furthermore, the current cost of ADCs can be limiting their reach. Here, we review the structure and functions of ADCs, as well as ongoing clinical investigations into novel ADCs and their potential as treatments of solid malignancies.
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Isolated mesenteric vein thrombosis associated with Fusobacterium is rare. Physicians should be aware regarding the association of Fusobacterium with thrombosis at various sites.
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Extragonadal parasitic dermoid cysts are rare. Diagnosis of such extragonadal parasitic teratoma is often done intraoperatively during surgical exploration of abdominal mass.
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BACKGROUND: Waldenström macroglobulinemia is a rare hematological malignancy and is the most common diagnosis in patients with hyperviscosity syndrome. Bilateral central retinal vein occlusion as an initial presentation of hyperviscosity syndrome in Waldenström macroglobulinemia is rare. CASE PRESENTATION: A 42-year-old Nepalese male presented with sudden-onset bilateral painless blurring of vision. Fundus examination revealed bilateral, diffusely dilated, tortuous retinal veins and intraretinal deep blot hemorrhages in all four quadrants of the retina in both eyes; features of bilateral central retinal vein occlusion. Serum electrophoresis showed hypoalbuminemia with an immunoglobulin M kappa monoclonal spike. Bone marrow picture and immunohistochemistry analysis were suggestive of lymphoplasmacytic lymphoma. The patient received systemic therapy for Waldenström macroglobulinemia, along with intravitreal bevacizumab. CONCLUSION: Adequate hydration, plasmapheresis, and a combination of bortezomib, dexamethasone, and rituximab regimen as a systemic therapy may represent an ideal choice for patients with hyperviscosity in Waldenström macroglobulinemia.
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Oclusão da Veia Retiniana , Macroglobulinemia de Waldenstrom , Humanos , Masculino , Adulto , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/etiologia , BortezomibRESUMO
Light chain (AL) amyloidosis is a lethal form of systemic amyloidosis that arises from the clonal expansion of CD38+ plasma cells. Organ damage occurs when these plasma cells produce misfolded immunoglobulin light chains, which form amyloid fibrils and deposit in tissues. A minority of patients with AL amyloidosis show "raccoon eyes" caused by increased vascular fragility from accumulation of amyloid fibrils. Amyloidosis can be directly associated with bleeding diathesis due to factor X deficiency as factor X binds to amyloid fibrils primarily in the liver and spleen. A 65-year-old Caucasian male presented with random bruising in the upper chest and around the eyes for 1.5 years. Physical examination was unremarkable, except for neck bruising. Pertinent workup showed protein electrophoresis with a faint M spike, increased serum lambda light chains, a kappa to lambda ratio of 0.06, increased Bence-Jones proteins, reduced factor X activity, elevated NT-proBNP. The bone marrow biopsy was positive for Congo red stain for amyloid protein. Magnetic resonance imaging revealed diffuse enhancement of the right and left ventricle subendocardial late gadolinium, consistent with cardiac amyloidosis. The patient started systemic therapy with a regimen of daratumumab, cyclophosphamide, bortezomib, and dexamethasone. After one cycle of therapy, lambda light chains normalized with an improvement in bruising. Diagnostic delays for cardiac patients are concerning as the median survival rate among these patients, when not treated, is approximately 6 months after the onset of symptoms. Since timely treatment can prevent organ damage, clinicians should be aware of specific clinical signs such as raccoon eyes and the importance of systemic evaluation for a prompt diagnosis.
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BACKGROUND: An acute abdomen can have a variety of causes. A commonly missed cause of abdominal pain is direct substance abuse and its sequelae. The use of methamphetamine is rising in the United States resulting in significant morbidity and mortality. There has been no reported case of methamphetamine-induced adrenal infarction based on an extensive review of available literature. CASE PRESENTATION: We present a case of a 34-year-old Hispanic man who presented with acute abdominal pain secondary to adrenal infarction in the setting of methamphetamine use. Left paraumbilical tenderness was present on abdominal examination. Contrast-enhanced CT of the abdomen and pelvis revealed internal hypoenhancement of the left adrenal gland, consistent with acute left adrenal infarction. The patient was managed with enoxaparin and apixaban. CONCLUSION: Substance abuse, especially among young patients, can at times present with acute abdomen. This mandates physicians to be vigilant and take into consideration the history of substance abuse and relevant investigations. Timely diagnosis and management can prevent life-threatening complications.
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Abdome Agudo , Traumatismos Abdominais , Doenças das Glândulas Suprarrenais , Metanfetamina , Masculino , Humanos , Adulto , Metanfetamina/efeitos adversos , Enoxaparina , Doenças das Glândulas Suprarrenais/diagnóstico , Traumatismos Abdominais/complicações , Dor Abdominal/induzido quimicamente , Infarto/induzido quimicamente , Infarto/diagnóstico por imagemRESUMO
Background: Universal access to essential medicines and routine diagnostics is required to combat the growing burden of cardiovascular disease (CVD) and diabetes. Evaluating health systems and various access dimensions availability, affordability, accessibility, acceptability, and quality is crucial yet rarely performed, especially in low- and middle-income countries. Objective: To evaluate health system capacity and barriers in accessing diagnostics and essential medicines for CVD and diabetes in Nepal. Methods: We conducted a WHO/HAI nationally-representative survey in 45 health-facilities (public-sector: 11; private-sector: 34) in Nepal to collect availability and price data for 21 essential medicines for treating CVD and diabetes, during MayJuly 2017. Data for 13 routine diagnostics was obtained in 12 health facilities. Medicines were considered unaffordable if the lowest paid worker spends >1 days wage to purchase a monthly supply. To evaluate accessibility, we conducted facility exit interviews among 636 CVD patients. Accessibility (e.g., private-public health facility mix, travel to hospital/pharmacy) and acceptability (i.e. Nepals adoption of WHO Essential Medicine List, and patient medication adherence) were summarized using descriptive statistics, and we conducted a systematic review of relevant literature. We did not evaluate medicine quality. Results: We found that mean availability of generic medicines is low (<50%) in both public and private sectors, and less than one-third medicines met WHOs availability target (80%). Mean (SD) availability of diagnostics was 73.1% (26.8%). Essential medicines appear locally unaffordable. On average, the lowest-paid worker would spend 1.03 (public-sector) and 1.26 (private-sector) days wages to purchase a monthly supply. For a person undergoing CVD secondary preventive-interventions in the private sector, the associated expenditure would be 7.511.2% of monthly household income. Exit-interviews suggest that a long/expensive commute to health-facilities and poor medicine affordability constrain access. Conclusions: This study highlights critical gaps in Nepals health system capacity to offer basic health services to CVD and diabetes patients, owing to low availability, poor affordability and accessibility of essential medicines and diagnostics. Research and policy initiatives are needed to ensure uninterrupted supply of affordable essential medicines and diagnostics.
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Doenças Cardiovasculares , Diabetes Mellitus , Medicamentos Essenciais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , NepalRESUMO
Dengue fever and scrub typhus are common causes of acute febrile illness of unclear origin in Asia. Though coinfections of many vector-borne diseases have been described, articles on dengue and scrub typhus coinfection are distinctly limited. In case of coinfection with dengue and scrub typhus, vigilant monitoring of vitals, platelets transfusion, and timely treatment with doxycycline are necessary. High degree of suspicion has to be made for coinfection in a patient presenting with febrile illness with thrombocytopenia and deranged laboratory parameters in postmonsoon season in endemic regions in Asia.