Answer:

This patient has a red flag in their HPI - cisplatin, which is very ototoxic. But, it is also important to not succumb to early closure. First, categorize hearing loss as conductive or sensorineural with the Weber and Rinne test.

Etiology: Is this normal hearing loss of old age (presbycusis)? With increasing age we will experience a symmetric, sensorineural hearing loss that is most pronounced at higher frequencies. This makes it difficult to hear consonants, which are higher pitched. The classic complaint is the inability to hear a conversation – especially in the presence of background noise. An elderly patient presenting with slowly progressive, symmetric, sensorineural hearing loss very likely has presbycusis.

Is this just cerumen impaction? If so, your Weber and Rinne tests should be consistent with just conductive hearing loss that will improve with cerumen removal.

If things are any more complicated or uncertain than the two textbook cases above, you need a formal audiogram.

From here, it is hard to provide a detailed algorithm, but some additional general pearls are:

Sensorineural hearing loss? – Don’t forget the basics. Check Hb1c, CBC for evidence of WBC dyscrasia (multiple myeloma), TSH, and syphilis.

As usual don’t forget adverse effects from medications. The following are some specific meds or groups of meds that are associated with ototoxicity: antibiotics (aminoglycosides specifically), chemotherapy (especially cisplatin), high dose aspirin, and loop diuretics.

Asymmetric sensorineural hearing loss? – check for vestibular schwannoma with an MRI w/contrast.

Unexplained conductive hearing loss? – consider temporal bone CT scan

While this patient does not yet meet criteria for severe neutropenia as we often learn it (ANC < 500), this is where the importance of predicting disease course is important. A second definition of severe neutropenia is if the ANC is expected to fall <500 within 48 hours. The WBC nadir post-chemotherapy (carboplatin in this case) is between 7-9 days, so this patient’s ANC should be expected to continue to decline and they should be treated as neutropenic fever. Their MASCC Score is 21 which puts them at high risk for complications and should be treated as an inpatient.

While this patient is at risk for many different infections the biggest initial concern is gram-negative sepsis as a large contributor to neutropenic fever is gut translocation due to the breakdown of mucosal barriers from the chemotherapy or malignancy. Vancomycin should be added in specific situations: concern for port/line infection, known colonization with MRSA, gram positive bacteremia, septic shock, evidence of soft tissue infection, mucositis (concern for Strep. Viridans infection).

While you are treating this patient, the next concern should be if the diagnosis is correct. Since this patient is also on a checkpoint inhibitor, there is always concern for various ‘itises’ - colitis, pneumonitis, hypophysitis, etc. He may require more localization of symptoms with history and imaging if there is concern.

Answer:

Hypertension is such a common co-morbidity that we often do not give it the evaluation that it deserves. Initially, this patient’s hypertension would likely be attributed to the headaches and pain from cancer and chemotherapy. But as the hypertension is persistent it needs to be addressed. Additionally, this is a fairly young patient without too much of a past medical history who presented with hypertension which should trigger a secondary hypertension evaluation - starting with the patient’s family history, doing a physical exam checking for thyroid issues, renal artery bruits, check for signs of Cushing, and mallampati class (and a STOP-BANG for OSA). I would order a renal panel looking for hypokalemia or metabolic alkalosis and a TSH looking for hypothyroidism. Getting a kidney ultrasound, an adrenal work up or renin-aldosterone levels would depend on pre-test probability. I would see if there are any behavioral causes - is this patient consuming vast quantities of salt or cocaine? Finally, I would check to see if there are any iatrogenic causes - this is especially true in any patient on medications I am not familiar with.

VEGF Inhibitors are commonly associated with hypertension, up to 87% in some studies! This is clinically significant hypertension with an increase in heart failure rates as well. The proposed mechanism is increased endothelin-1 production, leading to vasoconstriction.

Answer:

Re-framed, this is patient with a history of a thrombophilic cancer who presented with respiratory symptoms which should always be concerning for a pulmonary embolism. The patient is significantly hypoxic and mildly tachycardic - whether that is reflex from hypoxia or related to an underlying pathology is unclear. Hypoxia is not a common sign in PE, and as you can see it is not in the Well’s Score, and is related to intrapulmonary shunting and V/Q mismatch (if that is confusing go back to the respiratory failure half day). This patient should get a CTPA, which in this case does not show a large PE but bilateral GGO.

This patient is at risk for typical infectious pathologies and should get a COVID-19, RVP, Blood Cultures, sputum cultures, and should get broad spectrum antibiotics. However, one of the main concerns with this patient is an iatrogenic PD-1 inhibitor mediated pneumonitis. T-Cells are stimulated by an antigen, they must also be co-stimulated by other signalling proteins. The Programmed-Death Ligand is present on normal cells and inhibits T-Cells that inadvertently bind to normal cells. This PD-L1 protein is blocked by checkpoint inhibitors allowing them to ideally destroy cancer cells, but in some cases normal tissue - causing pneumonitis, colitis, hypophysitis, and others. This should be treated with steroids (1mg/kg prednisone) once infection is ruled out.

A meta analysis of clinical trials showed the risk of pneumonitis to be: All‐grade: OR = 6.29, 95% CrI: 2.67‐16.75; high‐grade: OR = 5.95, 95% CrI: 2.35‐17.29), pembrolizumab (all‐grade: OR = 5.78, 95% CrI: 2.79‐13.24; high‐grade: OR = 5.33, 95% CrI: 2.49‐12.97), and nivolumab plus ipilimumab therapy (all‐grade: OR = 14.82, 95% CrI: 5.48‐47.97; high‐grade: OR = 15.26, 95% CrI: 5.05‐55.52)

Answer:

When first evaluating this patient, the main thing to identify is whether or not they are stable. A heart rate of 140 rarely causes hemodynamic collapse. It is reasonable to treat this patient in the clinic with either diltiazem or metoprolol prior to sending them to the ED for further evaluation.

Next, I would want to evaluate this patient’s risk factors for afib and I would divide her risks into cardiac, pulmonary, and iatrogenic. When thinking about cardiac risk factors, I think about things that cause scars and things that stretch the myocardium - i.e. acute myocardial infarctions, valvular disease, and heart failure. Pulmonary risk factors are harder to find identify - but it is unclear if she has any underlying pulm disease from smoking, she could have OSA or even ILD from her RA which leads to pulmonary hypertension and increased afib risk.

While CLL is not commonly associated with afib (if you cannot recall the complications of CLL, revisit the hematologic malignancy half day), ibrutinib is. In multivariable analysis, patients treated with ibrutinib were associated with a 5-fold increased risk of developing atrial fibrillation (odds ratio = 5.18, 95% confidence interval 1.42 to 18.89). Make sure to message her oncologist because she will require at the very least a dose reduction of her ibrutinib if not a change in modality.