Prolonged Disease Control Despite ALK Inhibitor Discontinuation in Advanced ALK-Positive NSCLC.

Introduction: EML4-ALK is an oncogenic driver, seen in around five per cent of advanced non-small-cell lung cancer (NSCLC) patients, which can be targeted with anaplastic lymphoma kinase tyrosine kinase inhibitors with great response rates. Disease flare refers to sudden rapid disease worsening on tyrosine kinase inhibitors (TKI) discontinuation, which is associated with shorter survival and worse outcomes. Here, we review cases previously published in the literature where patients developed disease flares, and contrast this with our patients who had prolonged survival despite TKI discontinuation. Case description: We report three different patients with advanced ALK-positive NSCLC seen at our institute, who had EML4-ALK translocation variant 1 oncogenic driver on next-generation sequencing. They received treatment with several different ALK inhibitors before opting to discontinue TKI. They were able to come off TKI safely without developing disease flare and had prolonged survival. Discussion: Shorter time to progression on TKI, presence of symptoms with disease progression or central nervous system/pleural metastasis have been previously linked with development of flare, although this was not seen in our case series. Tumour response at the time of treatment discontinuation, line of therapy, overall disease burden, fusion variant and co-alteration status can affect the prognosis of these patients after ALK TKI cessation. In particular, variant 1 and wild-type TP53 status may be a suitable patient population for dose optimisation strategies. Intermittent TKI dosing strategies may help to avoid acquiring resistance mutations and prevent long-term treatment toxicities. Conclusion: It is important for clinicians to identify patients at risk for developing disease flare on TKI discontinuation to improve outcomes. Intermittent TKI dosing strategies require further investigation. LEARNING POINTS: Patients who develop disease flare after cessation have poor survival and worse outcomes.Certain phenotypic and molecular characteristics of the tumour may help clinicians identify which patients are likely and which are unlikely to develop disease flare on TKI discontinuation.Advanced ALK-positive NSCLC with variant 1 and wild-type TP53 may be a suitable patient population for intermittent TKI dosing investigations.

Extramedullary chronic lymphocytic leukemia disguised as urinary tract infection.

Extramedullary and nonlymphoid organ involvement in chronic lymphocytic leukemia (CLL) is exceedingly rare, with only a few cases of bladder infiltration reported to date. Here, we present a case of a 71-year-old man with advanced-stage CLL who presented with gross hematuria initially thought to be secondary to a urinary tract infection. However, a cystoscopy with biopsy confirmed the diagnosis of extramedullary CLL with bladder involvement. The patient was started on venetoclax with improvement in symptoms and no recurrence of hematuria.

Acquired Amegakaryocytic Thrombocytopenia Progressing to Aplastic Anaemia.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disorder of the bone marrow characterized by a lack of megakaryocytes and preservation of other cell lines. It can occur due to an intrinsic stem cell defect or secondary to viral infections, autoimmune disorders, lymphoproliferative disorders or environmental toxins. With time, it can progress to aplastic anaemia (AA) and can have a poor prognosis. No standard guidelines exist for the treatment of AAMT progressing to AA. Herein, we report a rare case of AAMT leading to AA and review the handful of cases previously published in the literature. LEARNING POINTS: Acquired amegakaryocytic thrombocytopenia can present as isolated severe thrombocytopenia which can initially be misdiagnosed as immune thrombocytopenia.Lack of response to steroids and intravenous immunoglobulin should raise suspicion for acquired amegakaryocytic thrombocytopenia.Over time, acquired amegakaryocytic thrombocytopenia can progress to aplastic anaemia, which confers a worse prognosis.

Angioimmunoblastic T-cell lymphoma with exuberant plasmacytosis and spontaneous tumor lysis syndrome.

We present a 67-year-old man with complaints of confusion, chills, night sweats, and several days of poor oral intake. He had severe plasmacytosis on lab work, which initially raised concern for plasma cell leukemia. However, further workup led to the diagnosis of angioimmunoblastic T-cell lymphoma. His initial hospital course was complicated by spontaneous tumor lysis syndrome. Early recognition and prompt interventions are pivotal to improve survival outcomes in such patients.

The Impact of Atrial Fibrillation on hospitalization Outcomes for Patients With Chronic Lymphocytic Leukemia Using the National Inpatient Sample Database.

BACKGROUND: The incidence of atrial fibrillation (AF) in patients with chronic lymphocytic leukemia (CLL) has been on the rise. However, the excess burden added by AF to the morbidity and mortality of CLL patients especially in the hospitalized setting is undetermined. METHODS: The National Inpatient Sample (NIS) database was accessed to gather data of hospitalized CLL patients with AF from 2009 to 2018. Propensity-score matching (PSM) and logistic regression model were performed to control for baseline patient factors to match 7265 CLL patient admissions with AF and 7265 CLL patient admissions without AF. The primary outcome was all-cause mortality (ACM), while the secondary outcomes included acute coronary syndrome (ACS), acute myocardial infarction (AMI), and the need for percutaneous coronary intervention (PCI), acute heart failure (AHF), acute hypoxic respiratory failure (AHRF), cardiac arrest (CA), cardiogenic shock (CS), stroke, and the total cost of hospitalization. RESULTS: CLL patients with AF had a higher rate of ACM (6.06% vs 4.47%; odds ratio [OR] 1.39, 95% confidence interval [CI] 1.19-1.61; P =< .001). All other secondary outcomes including ACS, AMI, PCI, AHRF, CA, CS, and stroke were observed at a significantly higher rate in the AF group as well. The median total hospital cost was also higher in the AF group ($9097 vs. $7646; P value < .0001) CONCLUSION: CLL patients with AF are at a significantly increased risk of all-cause mortality, cardiac-related mortality, and stroke. For this population, a multidisciplinary approach should be orchestrated for better management and outcomes.

Effect of physical activity and vitamin D compared with vitamin D alone on muscle strength, back flexibility and aerobic activity in patients with chronic kidney disease: A comparative study from Pakistan.

BACKGROUND AND OBJECTIVES: To compare the differences in musculoskeletal health with vitamin D alone in comparison with vitamin D with physical activity (PA) among chronic kidney disease (CKD) patients. METHODS AND STUDY DESIGN: An open labeled, randomized, controlled trial was conducted at two tertiary care centers in Pakistan. Patients with CKD stage 2-4 and vitamin D deficiency (<20 ng/mL) were recruited in the trial. Both the arms were given oral vitamin D (cholecalciferol) drops (4000 IU) once daily for three months. One arm received only vitamin D (VD arm), while the second arm received vitamin D along with PA (VDPA arm). RESULTS: Of the 1,235 CKD stage 2-4 subjects contacted, forty-six subjects were enrolled. Eighteen were assigned to VD arm and twenty-eight were assigned to VDPA arm. Between groups comparison shows that bicep strength increases from 15 to 17 kg. Likewise, back flexibility and aerobic fitness also increased among those who receive vitamin D and physical activity, however these differences were not statistically significant (p>0.05). Sensitivity analysis within group comparison shows rise of bicep strength from 13.8 kg to 15.2 kg in the VD alone arm (p=0.05); however, in the VDPA arm, there is a greater difference of 14.3 kg to 17.2 kg (p<0.001). CONCLUSIONS: Targeted PA among CKD patients has potential to improve bicep strength and back flexibility. However, as the sample size was small, further studies would be required to suggest whether a PA should be included as part of the treatment regimen.

Leg ulcer with long-term hydroxyurea use.

Long-term use of hydroxyurea can cause leg ulcers which usually do not heal unless the drug is discontinued. Patients should be counseled regarding alternative lines of treatment like anagrelide and pegylated-interferon.

Adenovirus-Associated Disseminated Intravascular Coagulation.

A 21-year-old previously healthy Caucasian female presented to the emergency department (ED) in the pre-COVID-19 era for evaluation of thrombocytopenia after a flu-like illness. The patient reported fever, cough, headache and myalgias for one week. She was on oral contraceptive pills (OCPs) for five years but discontinued one week ago. She was found to be in disseminated intravascular coagulation (DIC) and her hospital course was complicated by intraparenchymal hemorrhage, deep vein thrombus (DVT) in the right arm veins, bilateral pulmonary embolus (PE) and multiple splenic infarcts. An extensive workup was negative but nasopharyngeal swab came back positive for adenovirus by polymerase chain reaction (PCR).

Anaplastic Large Cell Lymphoma Presenting as Haemophagocytic Lymphohistiocytosis with Underlying Coxiella burnetii and Bartonella henselae Seropositivity.

A 44-year-old woman with no significant medical history presented with a 3-week history of high-grade fevers, fatigue and shortness of breath. Laboratory investigation was significant for lymphopenia and thrombocytopenia which progressively worsened during her hospital stay, along with new-onset anaemia, and elevated ferritin, transaminase and triglycerides. A computerized tomography (CT) scan of the abdomen revealed retroperitoneal lymphadenopathy. A bone marrow biopsy confirmed the diagnosis of haemophagocytic lymphohistiocytosis (HLH). Extensive infectious work-up revealed high IgG titres for Bartonella henselae and Coxiella burnetii. Interestingly, the left supraclavicular node was negative for both microbes by polymerase chain reaction (PCR), but the biopsy revealed anaplastic large T-cell lymphoma. LEARNING POINTS: Haemophagocytic lymphohistiocytosis (HLH) is an important differential diagnosis to consider for fever of unknown origin in adults, especially in the setting of pancytopenia and hyperferritinaemia.Q fever resulting from Coxiella burnetii can cause HLH and is also postulated to increase the risk of lymphoma.Bartonella henselae infection can also trigger HLH, but the risk of lymphoma following infection by B. henselae is unknown.

Metastatic Lung Adenocarcinoma With Occult Involvement of Gluteal Muscles as the Sole Site of Distant Metastases.

Lung cancer metastases to soft tissues are rarely reported in the literature. In this report, we discuss a case of a 59-year-old female who presented with worsening shortness of breath for over five months. A CT scan of the chest revealed right upper lobe mass and ipsilateral mediastinal adenopathy. An endo-bronchial ultrasound (EBUS)-guided biopsy of the involved lymph nodes revealed cellular features consistent with lung adenocarcinoma. MRI of the brain was negative for metastases; however, a positron emission testing (PET) scan showed fluorodeoxyglucose (FDG)-avid nodules in the soft tissues of the bilateral buttocks. Tissue biopsy of the buttock lesions confirmed metastases of lung origin. To the best of our knowledge, this is the first case report of metastatic lung adenocarcinoma with occult involvement of the gluteal muscles as the sole site of distant metastasis.

Hepatosplenic T-Cell Lymphoma in an Immunocompetent Young Male: A Challenging Diagnosis.

Hepatosplenic T-cell lymphoma is a rare but highly aggressive form of T-cell malignancy. As cases are not routinely seen in practice, the malignancy can be confused with other hematologic conditions that have a similar presentation. Here in, we present the challenges faced in diagnosing a 27-year-old-male who initially presented with asymptomatic pancytopenia and then developed massive splenomegaly over the next three months. After an elaborate workup, including a bone marrow biopsy and extensive serological testing, which all turned out to be negative, he eventually underwent a splenectomy with biopsy results confirming hepatosplenic T-cell lymphoma.

Suspected Metformin-induced Cobalamin Deficiency Mimicking Thrombotic Thrombocytopenic Purpura.

Thrombotic thrombocytopenic purpura (TTP) can often be life threatening and requires timely diagnosis and prompt initiation of plasmapharesis. Cobalamin deficiency can closely mimic TTP and distinguishing between the two diseases can prove to be a diagnostic challenge. Previously, cobalamin-related pseudo-TTP has been associated with pernicious anemia, dietary insufficiency and hereditary disorders of cobalamin activation. Here in, we discuss the first case of suspected metformin-induced cobalamin deficiency causing pseudo-TTP. Our patient was a 36-year-old female with type 2 diabetes mellitus on metformin for eight years who presented with hemolytic anemia, thrombocytopenia, schistocytes and mild acute renal failure. The initial impression was TTP; however, further workup revealed very low serum cobalamin levels and elevated methylmalonic acid levels. Apart from metformin use, no other cause of cobalamin deficiency was identified. We recommended upper gastrointestinal endoscopy to definitively rule out pernicious anemia.

Spontaneous tumor lysis syndrome in squamous cell carcinoma of the lung.

Tumor lysis syndrome (TLS) is an oncologic emergency, more commonly occurring in patients with hematologic malignancies receiving cancer-directed therapy due to massive cellular breakdown. Spontaneous TLS is rare and occurs in the absence of cancer-directed therapy. Herein, we present a case of spontaneous TLS associated with squamous cell carcinoma.

Uterine Transplant: A Risk to Life or a Chance for Life?

Being inherently different from any other lifesaving organ transplant, uterine transplantation does not aim at saving lives but supporting the possibility to generate life. Unlike the kidneys or the liver, the uterus is not specifically a vital organ. Given the non-lifesaving nature of this procedure, questions have been raised about its feasibility. The ethical dilemma revolves around whether it is worth placing two lives at risk related to surgery and immunosuppression, amongst others, to enable a woman with absolute uterine factor infertility to experience the presence of an organ enabling childbirth. In the year 2000, the first uterine transplantation, albeit unsuccessful, was performed in Saudi Arabia from where it has spread to the rest of the world including Sweden, the United States and now recently India. The procedure is, however, still in the preclinical stages and several ethical, legal, social and religious concerns are yet to be addressed before it can be integrated into the clinical setting as standard of care for women with absolute uterine factor infertility.

Russell's Viper Envenomation-Associated Addisonian Crisis.

Snakebite envenomation is an important public health problem in tropical countries. We report a case of bilateral adrenal hemorrhage in a 28-y-old man with Russell's viper bite that occurred in the Sathyamangalam forest range in the Indian state of Tamil Nadu. In this case, a combination of early bite recognition, hospital-based supportive care, corticosteroid therapy, and timely administration of polyvalent antivenom resulted in a favorable clinical outcome.

Cerbera odollam toxicity: A review.

Cerbera odollam is a plant species of the Apocynaceae family. It is often dubbed the 'suicide tree' due to its strong cardiotoxic effects, which make it a suitable means to attempt suicide. The plant grows in wet areas in South India, Madagascar, and Southeast Asia; and its common names include Pong-Pong and Othalanga. The poison rich part of the plant is the kernel which is present at the core of its fruit. The bioactive toxin in the plant is cerberin, which is a cardiac glycoside of the cardenolide class. Cerberin has a mechanism of action similar to digoxin; hence, Cerbera odollam toxicity manifests similar to acute digoxin poisoning. Ingestion of its kernel causes nausea, vomiting, hyperkalemia, thrombocytopenia, and ECG abnormalities. Exposure to high doses of Cerbera odollam carries the highest risk of mortality. Initial management includes supportive therapy and administration of atropine followed by temporary pacemaker insertion. Administration of digoxin immune Fab may be considered in severe cases, although efficacy is variable and data limited to isolated case reports.

Breaking your heart-A review on CPR-related injuries.

Cardiopulmonary resuscitation (CPR) has been shown to increase survival after cardiac arrest, but is associated with the risk of acquired injuries to the patient. While traumatic chest wall injuries are most common, other injuries include upper airway, pulmonary and intra-abdominal injuries. This review discusses the risk factors and prevalence of CPR-related injuries.