I first read Davidson 30 years ago: at that time it was already in its 5th edition. A brief comparison shows that it then contained about 440,000 words in 1,100 pages: the current edition has compressed 625,000 words into 800 pages. I think I bought it as a student because it was cheap: but also because it seemed to be comprehensive and straightforward, and I have used it as a basis for my medical knowledge ever since. So I miss some of the old pictures of the acute skin rashes such as scarlet fever: in fact infectious disease has been transferred to the back and genetic factors take the first chapters. But careful linguistic comparison will still uncover the old phrases which some of us know by heart-there are minor changes such as 'alarming reactions to intravenous iron are uncommon, but have occasionally been noted', which becomes 'alarming systemic anaphyllactic reactions can occur'. Sir Stanley Davidson made 'no attempt to describe every rare disease or syndrome, but devoted most of the space available to those disorders most commonly encountered in practice'. I have grown up with successive editions, and have gradually come to appreciate the problems of the authors in the compression of knowledge. Having got to know many of them personally as real people rather than as names I can still recommend the book. It is the essential starting point for the study of internal medicine and for many doctors will remain their base reference work. The present editors have kept up-to-date and been prepared to prune the dead wood. There are many competitors in the market, and the publishers must take care with layout and illustration, although Davidson is still the best value for money. I will continue to recommend it to my clinical students: they will need to read it and know it to pass final MB. Postgraduates will need to remember the facts, but also to be able to place them in a broader perspective. The older consultant will still happily read it, and to get to know the authors themselves is really to complete your medical education. Dr John Macleod and his team have successfully kept alive the primary objective 'to provide a rational and easily comprehensible basis for the practice of medicine'. The book is economical in price and compact in size, but still contains the essential truths for the practice of good medicine.

Davidson's Principles and Practice of Medicine

Hyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.

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Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines.

https://www.kidney-international.org/article/S2157-1716(15)32142-0/pdf

Current treatment practice and outcomes. Report of the hyponatremia registry

Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: “fungi and CNS mycoses”, CNS fungal infections”, “fungal brain infections”, " fungal cerebritis”, fungal meningitis”, “diagnostics of fungal infections”, and “treatment of CNS fungal infections”. All were published in English with the majority in the period 2000–2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.

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Neuroinfections caused by fungi.

https://www.amjmed.com/article/S0002-9343(15)01049-9/pdf

Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion

Hyponatremia is one of the most commonly encountered electrolyte abnormalities occurring in up to 22% of hospitalized patients. Hyponatremia usually reflects excess water retention relative to sodium rather than sodium deficiency. Volume status and serum osmolality are essential to determine etiology. Treatment depends on several factors, including the cause, overall volume status of the patient, severity of hyponatremic symptoms, and duration of hyponatremia at presentation. Vasopressin antagonists like tolvaptan seem promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure. Low sodium concentrations cause cerebral edema, but the overly rapid sodium correction can also lead to iatrogenic cerebral osmotic demyelination syndrome. Demyelination may occur days after sodium correction or initial neurologic recovery from hyponatremia. The following case report analyzes the role of vasopressin antagonists in the treatment of hyponatremia and the need for daily dosing of tolvaptan and the monitoring of serum sodium levels to avoid rapid overcorrection which can result in osmotic demyelination syndrome (ODS).

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Unpredictable nature of tolvaptan in treatment of hypervolemic hyponatremia: case review on role of vaptans.

A Rare Case of Candida Brain Abscess Secondary to Metastatic Tongue Cancer on Initial Presentation

Clinical assessment (4Ts) followed by testing for Heparin/platelet factor 4 (HPF4) antibody in intermediate and high risk patients is the standard algorithm of pretest for Heparin induced thrombocytopenia (HIT), and the diagnosis is confirmed by serotonin releasing assay (SRA) in those who have positive antibodies. We conducted a retrospective analysis in a cohort of patients treated in a community hospital who had HIT antibody test by either ELISA or a rapid Particle Immunofiltration Assay (PIFA), regardless of their 4Ts scores. Among 224 patients, 17 had HIT. The PPV for those with a 4 T score ≥4 was 10.4%, which misdianosed 3 patients with HIT who tested positive for antibodies. Combining 4 T score ≥4 AND positive HIT antibody showed a PPV of 20.3% and a sensitivity of 70.6%, misdiagnosing 5 HIT patients. Using 4Ts ≥4 OR positive HIT antibody showed 100% sensitivity and 100% negative predictive value (NPV). The ELISA test had 100% sensitivity and 100% NPV, while the PIFA test missed 2 HIT patients, with sensitivity of 60% and NPV of 96.7%. Our results suggest that SRA testing should be conducted if a patient presents with a 4 T score ≥4 OR a positive HIT antibody, and antibody tests should be conducted for every patient suspected of HIT.

https://journals.sagepub.com/doi/pdf/10.1177/1076029620962857

Prediction of Heparin Induced Thrombocytopenia (HIT) Using a Combination of 4Ts Score and Screening Immune Assays.

A Rapid Heparin Antibody Detection Assay Performs Better Than 4T's Score in Predicting HIT Diagnosis: A Single Community Medical Center Retrospective Analysis

a liver transplant for nonalcoholic steatosis hepatitis 8 weeks before presentation. She presented with bilateral leg and hand swelling, shortness of breath, pleuritic chest pain, and lightheadedness. Her immunosuppressive regimen consisted of tacrolimus, mycophenolate, and prednisone which she was compliant with. She presented with vitals of 36.6 C, 99 BPM, 122/80 mm/Hg, 92% on room air, and 18 breaths per minute. Pertinent examination findings were jugular vein distension, bilateral crackles, decreased heart sounds, and 3+ bilateral pitting edema on the upper and lower extremities. A CBC, BMP, UA, and PT/PTT were within normal limits. A chest x-ray showed prominent pulmonary vasculature. A computed tomography thorax without contrast showed moderate pericardial effusions. An echocardiography showed moderate pericardial effusions with inversion of the right atrium and tricuspid Doppler respiratory variation suggestive of tamponade. There was no systolic or diastolic dysfunction. After these echocardiogram findings were reported, Kussmaul sign and pulsus paradoxus were checked and were positive. Infectious disease work up was negative which included HIV, hepatitis C, HHV-6, and CMV. She has no history of radiation, cardiac surgery, or previously known cardiac issues. The tacrolimus level (FK-506) was 59.4 ng/mL on presentation, and the high normal limit within the first 6 months should not be above 15 ng/mL. The anasarca and tamponade were most likely due to tacrolimus toxicity. On presentation, she was taking 10 mg twice a day, the symptoms resolved with a dose reduction to 5 mg twice a day. There is no association of tacrolimus and tamponade in the literature. There was no other reasonable cause of the tamponade. An ECHO showed a preserved ejection fraction, no diastolic dysfunction, and no valvular abnormalities. Edema in the hands and legs are known adverse effects of tacrolimus;1 however, this is a separate process from the tamponade. The pleuritic chest pain and the weakness was most likely secondary to the tamponade. There are documented case reports of sirolimus causing tamponade.2 Tacrolimus and sirolimus, both activate FK-B12 receptors.3 Sirolimus inhibits mTOR, and tacrolimus prevents the dephosphorylation of NF-AT.3 The etiology of the tamponade remains unclear, but there is more evidence suggesting that tacrolimus and sirolimus do indeed cause cardiac tamponade possibly related to FK-B12 activation. Further investigation of this topic is warranted.

Ishan Malhotra

Papers

Unpredictable nature of tolvaptan in treatment of hypervolemic hyponatremia: case review on role of vaptans.

A Rare Case of Candida Brain Abscess Secondary to Metastatic Tongue Cancer on Initial Presentation

Prediction of Heparin Induced Thrombocytopenia (HIT) Using a Combination of 4Ts Score and Screening Immune Assays.

A Rapid Heparin Antibody Detection Assay Performs Better Than 4T's Score in Predicting HIT Diagnosis: A Single Community Medical Center Retrospective Analysis

Syndrome of Inappropriate Antidiuretic Hormone Consecutive to treatment with Ciprofloxacin.