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BACKGROUND: The advent of immune checkpoint inhibitors (ICI) has brought about a significant transformation in the treatment of immunogenic tumors. On November 23, 2015, the United States Food and Drug Administration approved Nivolumab to treat metastatic renal cell carcinoma (RCC). We aimed to assess potential changes in the survival rates of patients with metastatic RCC at a population level after the approval of Nivolumab. METHODS: We used data from the latest version of the Surveillance, Epidemiology, and End Results (SEER) database which encompasses data up to the year 2020. We included patients with age ≥ 20 years who were diagnosed with 'distant' RCC from 2011 through 2020. Based on the approval of Nivolumab, the period from 2011 to 2020 was further grouped into 2011-2015 (pre-ICI era) and 2016-2020 (ICI era). RESULTS: The median overall survival (OS) was 8 months in the pre-ICI era compared to 11 months in the ICI era (log-rank test, χ2 = 102.53, p < 0.001). Patients diagnosed with metastatic RCC in the ICI era had a significantly lower risk of dying [Cox proportional Hazard Ratio of 0.77, 95 % CI (0.74-0.80)] compared to patients diagnosed in the pre-ICI era. Additionally, patients under the age of 75 had a lower risk of death compared to those aged 75 years or older. Patients who received chemotherapy (systemic therapy), radiotherapy, or surgery faced a significantly lower risk of mortality. Individuals with metastasis to the brain, bone, liver, or lung had a significantly higher risk of death than those without metastasis to these locations. Marital status also played a role, as married individuals had a significantly lower risk of death compared to those who were divorced, separated, or widowed at the time of diagnosis. Furthermore, income level influenced survival, with patients earning a median annual household income of more than USD 75,000 exhibiting a significantly lower risk of mortality compared to those earning between USD 50,000 and USD 74,000. There was no significant difference in survival observed between non-Hispanic blacks and non-Hispanic whites. CONCLUSION: The advent of immune checkpoint inhibitors has led to a substantial improvement in the median overall survival of individuals diagnosed with metastatic renal cell carcinoma.

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Intravenous immunoglobulin (IVIG) is used to treat immunodeficiency conditions, neuro-immunological, infection-related, autoimmune, and inflammatory disorders and is typically well tolerated. A hematological adverse reaction such as hemolytic anemia and neutropenia is known to occur with IVIG, which is usually transient and subclinical. However, severe hemolytic anemia is known to occur in some cases. We present a case of a 66-year-old man who developed severe symptomatic hemolytic anemia after receiving IVIG for acute inflammatory demyelinating polyneuropathy (AIDP). The patient had known risk factors such as non-O blood group, high cumulative dose of IVIG, and underlying autoimmune condition, which would have put him at high risk for developing hemolytic anemia after IVIG. Therefore, it is prudent for clinicians to have increased awareness regarding the potential for severe hemolysis and closely monitor these patients with risk factors after treatments to identify this adverse reaction before more severe complications occur.

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Background: The use of thromboelastography (TEG) has demonstrated decreased blood product utilization in patients with specific etiologies of major gastrointestinal bleeding (GIB), such as variceal and non-variceal bleeding in cirrhosis patients; however, in a non-cirrhosis patient with GIB, there is far less evidence in the literature. Our retrospective study compares the effect of TEG-guided blood product utilization in patients with major GIB with all etiologies, including cirrhosis, admitted to medical intensive care unit (MICU). Methods: A retrospective chart review was conducted on patients admitted to the MICU of a tertiary academic medical center diagnosed with GIB using ICD-9/10 codes from 2014 to 2018. A total of 1,889 patients were identified, and validation criteria such as "GI or hepatology consult note", type and screen, pantoprazole, or octreotide drip" were used, which resulted in 997 patients, out of which 369 had a diagnosis of cirrhosis. Propensity score matching was done for baseline variables (age, sex, and race), ICU length of stay, hospital length of stay, ventilator days, and vasopressor use. As a result, 88 patients were included in the final analysis, with 44 in TEG and 44 in non-TEG group. A sub-group analysis was done in 46 patients with cirrhosis, 23 in TEG group and 23 in non-TEG group after propensity score matching. Results: There was significantly higher total blood volume (4,207 mL vs. 2,568 mL, P = 0.04) in the TEG group as compared to the non-TEG group, including total volume of cryoprecipitate (80 mL vs. 55 mL, P = 0.03) and total volume of platelet (543 mL vs. 327 mL, P = 0.03). In the cirrhosis sub-group, there was no significant difference in the amount of blood products transfused between the two groups. Conclusion: This study revealed that TEG is not superior to conventional coagulation parameters in limiting the volume of blood product transfusion in major GIB patients in ICU settings.

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Methemoglobinemia is a rare blood disorder characterized by the oxidation of heme iron from ferrous (Fe2+) to ferric (Fe3+) state, which increases oxygen affinity and impairs oxygen release to the tissue causing hypoxia. It can be congenital or acquired; however, most cases are acquired and caused by exogenous substances such as medications, chemicals, and environmental substances. Phenazopyridine is an over-the-counter urinary analgesic medication commonly used for symptomatic relief of dysuria and has been reported to cause methemoglobinemia. However, only a handful of cases of phenazopyridine-induced methemoglobinemia have been reported. We present a case of an 89-year-old female who presented with severe hypoxia, shortness of breath, headache, nausea, and dizziness caused by phenazopyridine-induced methemoglobinemia. She was found to have a methemoglobin level of 21.5% and was treated with methylene blue, leading to a rapid improvement of her symptoms. She was taking one over-the-counter phenazopyridine 200 mg tablet three times daily for two weeks for her chronic dysuria. This case highlights the need to have a high index of suspicion of phenazopyridine-induced methemoglobinemia in a patient presenting with unexplained shortness of breath with a history of phenazopyridine use as it could lead to severe methemoglobinemia with hypoxia that could potentially be fatal if not promptly diagnosed.

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Introduction: mRNA COVID-19 vaccines are very safe, but rare adverse events such as transverse myelitis have been reported after COVID-19 vaccination. Case Description: We report the case of 50-year-old man who presented with progressive lower extremity weakness, back pain and urinary retention after his second dose of the Pfizer COVID-19 vaccine. MRI of the spine revealed longitudinally extensive transverse myelitis (LETM). He recovered completely after treatment with intravenous methylprednisone and physical therapy. Discussion: This case highlights the rare association between LETM and COVID-19 vaccines and encourages clinicians to maintain a high index of suspicion for prompt diagnosis and treatment. LEARNING POINTS: Longitudinally extensive transverse myelitis (LETM) is rare adverse events after mRNA COVID-19 vaccination.Clinicians should maintain a high index of suspicion for prompt diagnosis of vaccine-induced transverse myelitis.Vaccine-induced LETM should show marked clinical improvement after appropriate treatment.

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Denosumab is a human monoclonal antibody used to prevent skeletal-related events in prostate cancer patients with bone metastasis. Hypocalcemia ranging from mild to severe requiring prolonged hospitalization have been reported with the use of denosumab in patients with known risk factors such as chronic kidney disease, vitamin D deficiency, low parathyroid hormone level, hypomagnesemia, extensive osteoblastic metastasis, prior use of bisphosphonates, and comorbidities impairing calcium absorption. We present a case of a metastatic prostate cancer patient with extensive osteoblastic metastasis who developed severe recurrent hypocalcemia after a single dose of denosumab requiring a total of 58 days of high dose intravenous and oral calcium supplementations with three inpatient hospital admissions. This case highlights the risk of severe hypocalcemia associated with denosumab use even after the disease control with oncologic therapy and in the absence of other predisposing risk factors. This case also emphasizes monitoring calcium levels closely in all patients treated with denosumab. In the event of severe hypocalcemia, prolonged hospitalization should be expected, and discharge planning should be done meticulously, which may help decrease the overall length of hospital stay, readmissions, and morbidity.

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BACKGROUND Severe hypercalcemia is a life-threatening medical emergency. Its possible etiologies are hyperparathyroidism, malignancy, chronic granulomatous diseases, vitamin D intoxication, medication (lithium, thiazine, excessive vitamin A), hyperthyroidism, acromegaly, adrenal insufficiency, pheochromocytoma, milk-alkali syndrome, and immobilization. Dehydration is considered a consequence of hypercalcemia but not the etiology. CASE REPORT We present a case of a 50-year-old woman who presented with headache, nausea, dizziness, and profound weakness, with a serum calcium level of 17.3 mg/dL due to severe dehydration. The other causes of hypercalcemia were diligently excluded with extensive laboratory testing. The patient's calcium level improved with aggressive intravenous hydration. In the subsequent follow-up visits, the calcium level remained within the reference range. The pathophysiology of severe hypercalcemia caused by dehydration is not clear. However, a feedforward mechanism has been proposed to occur, which worsens both dehydration and hypercalcemia. Dehydration as an initial insult leads to mild or transient hypercalcemia due to decreased fluid volume that affects calcium excretion via the kidneys. Subsequently, hypercalcemia interferes with the kidney's ability to concentrate urine, leading to further dehydration. This sets up a vicious loop that worsens both dehydration and hypercalcemia, leading to profound dehydration and severe hypercalcemia. CONCLUSIONS Dehydration is considered a consequence of hypercalcemia but has not been identified as the etiology of severe hypercalcemia. Hyperparathyroidism and malignancy are the most common causes of severe symptomatic hypercalcemia, and dehydration is the diagnosis of exclusion. However, it is imperative to keep dehydration in the differential diagnosis for a patient presenting with severe symptomatic hypercalcemia, as highlighted by our case.

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Brucellosis typically presents with nonspecific symptoms of intermittent fever, night sweats, malaise, and arthralgia but can involve any organs as focal brucellosis. Intraabdominal involvement is rare. We report a case of acute cholecystitis associated with brucellosis with no history of exposure to risk factors in a non-endemic area.

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Mycoplasma pneumoniae (M. pneumoniae) is a common cause of community-acquired pneumonia. It has been associated with many extrapulmonary manifestations that can present even in the absence of pulmonary signs and symptoms. Rhabdomyolysis and central nervous system (CNS) manifestations are rare extrapulmonary manifestations. These are infrequently reported in adults. We present a case of a healthy 32-year-old male who initially presented with signs and symptoms of community-acquired pneumonia and was treated with antibiotics. However, he continued to have generalized malaise, night sweats, diffuse joint pain, and myalgias and was subsequently noted to have rhabdomyolysis with elevated creatine kinase (CK) and myoglobin levels. Rhabdomyolysis was attributed to M. pneumoniae based on the recent history of upper respiratory tract infection and M. pneumoniae immunoglobulin M (IgM) serology positivity along with high M. pneumoniae IgG titer. The other causes of rhabdomyolysis were diligently excluded based on patient history and laboratory and clinical data. This immune-mediated rhabdomyolysis improved with intravenous hydration, doxycycline, and prednisone therapy. However, the patient developed progressive weakness with neuropathy, which required treatment with intravenous immune globulin (IVIG). This case highlights the need to maintain a high index of suspicion for rare extrapulmonary manifestations of mycoplasma infection, which could be life-threatening or cause significant morbidity; and in cases of severe extrapulmonary manifestations, the appropriate use of immunosuppressive/immunomodulatory therapy may lead to a better outcome.

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Hepatitis-associated aplastic anemia (HAAA) is a rare clinical syndrome characterized by bone marrow failure 1-3 months after development of hepatitis. Untreated, hepatitis-associated aplastic anemia has poor outcome and the mainstay of treatment remains either bone marrow transplant or immunosuppressive therapy. A previously healthy 21-year-old man presented with a 1-week history of right upper quadrant pain and jaundice. Admission labs revealed mixed hyperbilirubinemia and elevated transaminases ranging in 2000s IU/dl. Extensive workup for etiologies of acute hepatitis including viruses, autoimmune, toxins etc. were negative. He admitted to taking "Dust V2," a workout supplement, for 4 months prior to the presentation. His liver function tests started to improve after conservative treatment. Two months after his discharge, he was found to have severe pancytopenia on routine labs. Bone marrow biopsy revealed hypocellular marrow consistent with aplastic anemia. Extensive workup for etiologies of aplastic anemia were negative. On literature review, none of the components of the supplement were found to cause aplastic anemia. A diagnosis of hepatitis-associated aplastic anemia was made as there was a lag time before development of anemia. His counts failed to improve despite treatment with filgrastim and he was referred for hematopoietic cell transplant.

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Catastrophic antiphospholipid syndrome (CAPS) is a rare but severe form of antiphospholipid syndrome (APS). The syndrome manifests itself as a rapidly progressive multiorgan failure that is believed to be caused by widespread micro-thrombosis. Seldom does bleeding comanifest with thrombosis. We present a patient with APS who presented with nausea, vomiting and fatigue, and rapidly progressed into multiorgan failure before being diagnosed with CAPS. The clinical course was complicated by an atraumatic intracranial haemorrhage which demanded discontinuation of anticoagulation. The patient was treated with high dose steroid, intravenous immunoglobulin, followed by weekly rituximab infusion. Although the trigger for CAPS was not obvious during her hospital stay, she was diagnosed with acute cytomegalovirus (CMV) infection soon after discharge. In this case report, we explore the differential diagnoses of CAPS, investigate the possibility of CMV infection as a potential trigger, present the therapeutic challenges of anticoagulation and discuss the emerging use of rituximab.

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Buschke-Löwenstein tumor of anorectal and perianal area is a rare but highly aggressive tumor, frequently associated with human papillomavirus (HPV) types 6 and 11. It often grows over years in immunocompetent patients and can be highly destructive to local tissue. We present a case of a 61-year-old male with HIV infection who presented with worsening pain and swelling in the anorectal area for one-year duration. Exam revealed a 15 × 10 cm mass in the anorectal area with multiple sinuses and fistulas. MRI revealed extension of the mass through pelvic structures. Biopsy showed squamous epithelium with koilocytes and histochemistry positive for P16, suggestive of HPV infection. Biopsy was negative for malignant transformation. He was not a candidate for surgery or radiation due to extensive infiltration of deeper structures and multiple fistulas. He refused interferon therapy, and diverting colostomy was placed for palliation. He presented two months later with overwhelming sepsis and died despite maximal medical therapy.