An Exuberant Case of Ulceronodular-Rupioid (Malignant) Syphilis in an HIV Patient: A Proposal for New Diagnostic Criteria.

We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark lamellated crusting on his face, torso, and limbs. The patient had a rapid plasma reagin (RPR) titer of 1:512, indicative of syphilis. A skin biopsy revealed granulomata surrounded by lymphocytes, histiocytes, and plasma cells, with spirochetes visible on immunohistochemical staining. The patient's rash resolved with hyperpigmented scarring after penicillin and doxycycline treatment. This severe form of secondary syphilis has been termed malignant syphilis, lues maligna, ulceronodular syphilis, or rupioid syphilis. We propose a single descriptive name for this entity, ulceronodular-rupioid syphilis. In 1969, Fisher proposed criteria for malignant syphilis based on lesion appearance, histopathologic findings, high RPR values, and rapid response to treatment. We found that the Fisher criteria were imprecise with respect to specific histopathologic findings, the quantitation of RPR values, and what constitutes rapid response to treatment. Thus, we examined an additional 74 cases from the literature and propose new diagnostic criteria based on rash appearance, histopathologic characteristics, non-treponemal and treponemal test positivity, and response to therapy. We also found that uncontrolled viremia, and not a low CD4 count, is a major risk factor for ulceronodular-rupioid syphilis in HIV patients.

Sensitivity and Specificity of a Novel Colony Characteristic for Determination of Methicillin-Resistant Staphylococcus aureus.

PURPOSE: To assess colony morphology of Staphylococcus aureus isolates for target shape (T1) and its utility in the identification of methicillin-resistant S. aureus (MRSA). METHODS: Staphylococcus species isolated from blood cultures were studied for colony morphology characteristics. A polymerase chain reaction (PCR) test was performed on positive blood culture bottles for the detection of S. aureus and methicillin resistance. Colony morphology was read at 24 and 48 hours and defined as follows: target shaped (T1) - an elevated colony center encircled by a pale zone, which is surrounded by a single ring of peripheral enhancement giving a 'target' appearance; dome-shaped (T2) with an elevated center lacking the 'target' appearance. RESULTS: At 48 hours, 73.7% of MRSA and 59.5% of coagulase-negative staphylococci (CoNS) showed T1 morphology. T1 morphology has a sensitivity of 73.68% and specificity of 93.55% amongst S. aureus for identification of methicillin resistance and a high positive predictive value (95.45%) at 48 hours. CONCLUSION: T1 morphology has a modest sensitivity with specificity and positive predictive value amongst S. aureus for identification of methicillin resistance at 48 hours. It can be potentially used for the identification of MRSA, especially in resource-limited settings and wherein a molecular test is not repeated if PCR testing has already identified methicillin-sensitive S. aureus (MSSA) on a recent specimen on the same patient.

Impact of Liver Biopsy Size on Histopathologic Evaluation of Liver Allograft Rejection.

CONTEXT.­: Allograft liver biopsy is the gold standard in assessing transplant recipients for graft dysfunction. The impact of biopsy sample size on the diagnosis of acute cellular rejection (ACR) has not been studied. OBJECTIVE.­: To assess the relationship of biopsy sample length with the diagnosis and determine optimal biopsy sample size in the transplant setting. DESIGN.­: We retrospectively reviewed 68 core biopsies from patients with a history of liver transplant. Each biopsy sample was read, on 5 different occasions with differing lengths, to assess for ACR per Banff criteria. Categorical agreement was calculated from rejection severity. RESULTS.­: The length of biopsy sample strongly correlated with the number of portal tracts. ACR rates increased from 73.5% to 79.4% with increase in length from 1 cm to 2 cm, and moderate rejection increased from 27.9% to 33.82%. At 1.0 and 1.5 cm, no cases of severe rejection were detected; at 2.0 cm, 1 case was detected; and at 3.0 cm, 2 cases were detected. The major error rate was reduced to less than 10% with a length of 2.0 cm, at which length the average number of complete and partial portal triads was 10 and 13, respectively. CONCLUSIONS.­: The likelihood of diagnosing ACR and rejection grade increased substantially with increase in biopsy sample length. This study suggests that a minimum length of 2 cm, 10 complete portal triads, or 13 partial/complete portal triads should be obtained for confident exclusion and grading of ACR.

Retropharyngeal abscess- An unusual complication in a COVID-19 patient.

The coronavirus disease 2019 (COVID-19) pandemic has generated many challenges for physicians, including multiple long-term effects that are still being studied. We report a CASE of patient who developed a retropharyngeal abscess post-COVID19 infection. We report a CASE of a female who was diagnosed with COVID19 pneumonia and hospitalized for a week at an outside institute. Approximately 3 weeks post discharge she developed neck pain, dysphagia, voice change and odynophagia for which she went to an outside emergency department. A soft tissue neck CT was performed and was concerning for retropharyngeal abscess. The patient was then transferred to our institution. On arrival, a CT scan of the neck and nasopharyngoscopy were performed and biopsies of the epiglottis and right inferior tonsillar pole were taken. Biopsies of the epiglottis and tonsil showed acute inflammation, spongiosis, edema and marked dilation of the lymphatics. Her clinical course was complicated by persistent infection requiring multiple washouts, hyperglycemia, tube feed intolerance, dysphagia and deconditioning. A multi-disciplinary approach was instituted for appropriate management. This case report highlights the necessity for close follow up after recovery from COVID-19 infection, particularly in patients with multiple comorbidities.

A Surprising Cause of Liver Abscesses in a Post-Chemotherapy Patient: Herpes Simplex Virus.

Herpes simplex virus (HSV) hepatitis is a rare complication of HSV infection, and a rare cause of hepatitis. It is often fatal, especially if the diagnosis and treatment are delayed. Herein, we describe the case of a 31-year-old female with a history of receiving cytotoxic cancer chemotherapy five months prior who presented with a one-week history of worsening abdominal pain and fever. She was noted to have an outbreak of genital herpes at the time of presentation. Computed tomography (CT) scan of the abdomen showed innumerable hypodensities compatible with hepatic micro-abscesses. A specimen from a subsequent liver biopsy revealed HSV-type cytopathic changes and nuclear staining with an anti-HSV immunohistochemical stain. She was initially started on high-dose oral valacyclovir for genital herpes and was noted to have rapid clinical improvement prior to the histopathologic diagnosis of HSV hepatitis. She achieved full recovery while on oral valacyclovir. This is the first reported case of HSV hepatitis treated with oral valacyclovir and the third reported case of HSV hepatitis mimicking pyogenic abscesses on abdominal imaging. With the high mortality rate associated with HSV hepatitis, one should consider the diagnosis in all patients with multifocal liver lesions of unknown etiology, especially if genital herpes is present at the time of presentation, or in patients who are immunocompromised.

Fatal coccidioidomycosis involving the lungs, brain, tongue, and adrenals in a cirrhotic patient. An autopsy case.

In this paper, we describe a case of fatal disseminated coccidioidomycosis (CM). The patient was a 44-year old male with a history of cirrhosis who presented with altered mental status, cough, and an enlarged, ulcerated tongue. On evaluation, the patient was found to have coccidioidal infection of the tongue, lungs, and brain. Despite over two months of antifungal treatment, the patient died from aspiration pneumonia and at autopsy was found to have persistent infection of the tongue and lungs, extensive mycosis of the brain, and involvement of both adrenal glands. The fulminant course of coccidioidomycosis in this patient is ascribed to his baseline cirrhosis and lymphocytopenia. There are few autopsy cases of CM that have been described in the post-antifungal era and few published cases of CM with either tongue or adrenal involvement.

Correlation of cerebellar granular layer autolysis with ante-mortem systemic acid-base status.

Research in neuroscience relies heavily upon postmortem human brain tissue. Cerebellar granular layer autolysis (GLA) is a surrogate marker for the quality of such tissue and suitability for molecular analysis. GLA is associated with reduced brain tissue pH. The aim of this study was to assess correlation of GLA with premortem systemic acid-base status. This is a retrospective study in which 62 consecutive adult autopsy cases were included. Sections of cerebellum were reviewed microscopically for presence of GLA. Autolysis was graded as negative, grade 1, grade 2, and grade 3. Medical records were reviewed for arterial blood gas analysis. Postmortem interval was recorded. 23 of 62 cases showed GLA. Of the 23 patients with autolysis, 22 were acidotic and 1 was alkalotic. Of these 23 cases, 15 had metabolic acidosis, 4 had respiratory acidosis, 3 had combined acidosis and 1 had respiratory alkalosis. There was no statistically significant difference in postmortem interval between the two groups. 10 cases with grade 3 autolysis had mean pH of 7.13, 7 cases with grade 2 autolysis had mean pH of 7.23 and in 6 cases with grade 1 autolysis the mean pH was 7.2. Overall, the mean pH in patients with GLA was 7.19, and in the non-autolytic cases the mean pH was 7.28 (P < 0.05). There was no correlation between the degree of acidosis and severity of autolysis. GLA is associated with premortem systemic acidosis, and premortem systemic alkalosis is associated with the absence of GLA. Premortem acid-base status may serve as an additional quality indicator for assessment of tissue for research.

Invasive Colonic Mucormycosis in an Immunocompromised Postliver Transplant Patient.

Mucormycosis (zygomycosis) is an invasive fungal disease caused by Rhizopus species, most commonly implicated in diabetic ketoacidosis and other immunocompromised states. This report presents a unique case of colonic mucormycosis in a patient several weeks after liver transplant. The patient's course was complicated by polymicrobial infection and intra-abdominal abscesses, ultimately leading to septic shock and death. This case is the first of its kind to describe such malignant abdominal mucormycosis in a solid organ transplant recipient.

Case Report: Early Doxycycline Therapy for Potential Rickettsiosis in Critically Ill Patients in Flea-Borne Typhus-Endemic Areas.

Flea-borne typhus (FBT), although usually perceived as a self-resolving febrile illness, actually encompasses a wide spectrum of disease severity, including fulminant sepsis with multi-organ failure. In endemic Texas and California, the incidence of FBT has more than doubled over the last decade. Clinicians remain unfamiliar with severe septic presentations of FBT when considering the etiologies of acute undifferentiated febrile syndromes. The diagnostic challenges of FBT include the nonspecific and variable nature of both history and physical examination and the lack of diagnostic testing that can provide clinically relevant information early in the course of infection. These barriers perpetuate misdiagnoses in critically ill patients and lead to delay in initiating appropriate antibiotics, which may contribute to preventable morbidity and mortality. This case series describes the clinical and diagnostic trajectories of three patients who developed FBT-associated multi-organ dysfunction. These patients achieved resolution of infection after receiving doxycycline in the context of a high clinical suspicion. Patients residing in FBT-endemic areas presenting with a febrile illness of unknown etiology with a suggestive constellation of hyponatremia, elevated transaminase levels, and thrombocytopenia should be suspected of having FBT. Clinicians should proceed to serologic testing with early doxycycline therapy for potential rickettsiosis. Familiarizing clinicians with the presentation of rickettsiosis-associated septic syndromes and its early and appropriate antibiotic treatment can provide lifesaving care and reduce health-care costs through prevention of the morbidity associated with FBT.

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy.

CONTEXT.­: Hepatic encephalopathy (HE) is associated with presence of type II astrocytes in the brain on the basis of observations made in single uncontrolled cases. This finding was subsequently demonstrated by in vitro studies with replication of microenvironment of HE by increase in ammonia levels. However, no human studies have been done correlating HE with type II astrocytes. OBJECTIVE.­: To determine the sensitivity and specificity of type II astrocytes in HE. DESIGN.­: This is a retrospective cohort study in which cases and controls were included. A database search was conducted to identify potential cases of hepatic encephalopathy during a 3-year period, as well as concomitant cases with altered mental status from other causes, liver disease, both, and neither. The presence of HE was determined according to standard clinical criteria, and a coronal section of basal ganglia was selected for examination from each case. Type II astrocytes were enumerated over 20 random high-power fields (HPFs). RESULTS.­: Twenty-one patients with HE were identified, with 35 patient controls (18 females, 38 males). Among the patients with HE there was a mean of 19.8 type II astrocytes in 20 HPFs. Patients with altered mental status without HE had an average of 7.2 type II astrocytes per 20 HPFs, and for those without altered mental status, the average was 2.8. For patients with hepatic insufficiency without HE, the average was 11, while for patients with normal hepatic function, the average was 4.1. Overall, for those without HE, the average was 5.4 type II astrocytes per 20 HPFs. CONCLUSIONS.­: At a cutoff of 5 or more type II astrocytes per 20 HPFs, sensitivity for HE was 85.7% and specificity was 68.6%. Alzheimer type II astrocytes were present in all cases of HE but were also present in a wide variety of patients without HE.

Case Report: Fulminant Murine Typhus Presenting with Status Epilepticus and Multi-Organ Failure: an Autopsy Case and a Review of the Neurologic Presentations of Murine Typhus.

Murine typhus (MT) is an important cause of febrile illness in endemic areas, and there is an epidemiologic resurgence of this infection currently transpiring in Texas and California. Fatal cases and severe neurological complications are rare. A fatal case of MT in a middle-aged man is reported with a course culminating in multi-organ failure and refractory status epilepticus. An autopsy revealed hemorrhagic pneumonia, acute tubular necrosis, and ischemic necrosis in the liver, adrenals, and brain. We have also reviewed the neurologic complications of MT.

Defective synthesis and release of astrocytic thrombospondin-1 mediates the neuronal TDP-43 proteinopathy, resulting in defects in neuronal integrity associated with chronic traumatic encephalopathy: in vitro studies.

Transactivating DNA-binding protein-43 (TDP-43) inclusions and the accumulation of phosphorylated and ubiquitinated tau proteins (p-tau) have been identified in postmortem brain specimens from patients with chronic traumatic encephalopathy (CTE). To examine whether these proteins contribute to the development of CTE, we utilized an in vitro trauma system known to reproduce many of the findings observed in humans and experimental animals with traumatic brain injury. Accordingly, we examined the role of TDP-43 and Tau in an in vitro model of trauma, and determined whether these proteins contribute to the defective neuronal integrity associated with CNS trauma. Single or multiple episodes of trauma to cultured neurons resulted in a time-dependent increase in cytosolic levels of phosphorylated TDP-43 (p-TDP-43). Trauma to cultured neurons also caused an increase in levels of casein kinase 1 epsilon (CK1ε), and ubiquitinated p-TDP-43, along with a decrease in importin-ß (all factors known to mediate the "TDP-43 proteinopathy"). Defective neuronal integrity, as evidenced by a reduction in levels of the NR1 subunit of the NMDA receptor, and in PSD95, along with increased levels of phosphorylated tau were also observed. Additionally, increased levels of intra- and extracellular thrombospondin-1 (TSP-1) (a factor known to regulate neuronal integrity) were observed in cultured astrocytes at early stages of trauma, while at later stages decreased levels were identified. The addition of recombinant TSP-1, conditioned media from cultured astrocytes at early stages of trauma, or the CK1ε inhibitor PF4800567 hydrochloride to traumatized cultured neurons reduced levels of p-TDP-43, and reversed the trauma-induced decline in NR1 subunit of the NMDA receptor and PSD95 levels. These findings suggest that a trauma-induced increase in TDP-43 phosphorylation contributes to defective neuronal integrity, and that increasing TSP-1 levels may represent a useful therapeutic approach for the prevention of the neuronal TDP-43 proteinopathy associated with CTE. Read the Editorial Highlight for this article on page 531.

Pseudofungi: A Diagnostic Pitfall.

Pseudofungi are septate hyphae-like structures very similar morphologically to true fungal elements. Histologically their presence poses a diagnostic challenge as they mimic fungal infection. Accurate identification of pseudofungi is required to avoid unnecessary treatment, and this can be accomplished by careful morphologic analysis with the use of appropriate histochemical stains. We report a patient with pseudofungi within a paratracheal lymph node, describe the morphologic findings, and discuss the differential diagnosis.

Immediate effect of scapular repositioning with active cervical rotation in acute spasmodic torticollis.

OBJECTIVES: The aim of this preliminary study was to investigate the immediate effects on pain and pressure pain threshold (PPT) of a scapular repositioning technique in patients with acute spasmodic torticollis. METHODS: A randomized, single blind pilot study was conducted. The subjects were 23 individuals (age 20-40 years) with a clinical diagnosis of spasmodic torticollis. Visual analog scale pain score, cervical active ranges of motion, and PPT were assessed before and after the intervention. The comparison group was treated with only conventional physiotherapy (microwave diathermy, submaximal isometrics, and ergonomic advice). The intervention group was given scapular repositioning with active cervical rotation technique, in addition to conventional physiotherapy treatment. RESULTS: There were significant improvements in intensity of pain (P < .01), cervical rotation to the ipsilateral side (P < .01), cervical side flexion to the contralateral side (P < .01), and PPT (P < .01) immediately after the treatment of the scapular repositioning and conventional therapy compared with the conventional therapy alone. CONCLUSION: The present pilot study demonstrated that scapular repositioning may have an immediate hypoalgesic effect on individuals with spasmodic torticollis in terms of pain severity, PPT, and cervical range of motion. Therefore, further controlled trials are warranted.