Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Two Head and Neck Carcinomas With Squamous and Mucinous Components and Human Papillomavirus Associations: Maxillary Mucoepidermoid Carcinoma ex Sinonasal Schneiderian Papilloma and Tonsillar Invasive Stratified Mucin Producing Carcinoma (ISMC).

Carcinomas of the head-and-neck region with squamous and glandular/mucinous features constitute a heterogeneous group, with a significant minority of tumors showing an human papillomavirus (HPV) association. The differential diagnosis is usually between mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma. We present here two tumors that exemplify both the challenges of diagnostic classification, as well as the complex relationship to HPV: (a) a low risk HPV positive/p16 negative carcinoma that is most consistent with a relatively typical intermediate grade mucoepidermoid type carcinoma with complete MEC phenotype (three cell types), originating from intranasal sinonasal papillomas with exophytic and inverted patterns, and invading surrounding maxillary compartments, and (b) a p16 and keratin 7 (KRT7) positive carcinoma of the right tonsil, characterized by stratified squamous and mucinous cell (mucocyte) features. Whereas the first tumor represents a typical MEC ex-Schneiderian papilloma, the second is morphologically most consistent with the, novel for this anatomic location, diagnosis of "invasive stratified mucin producing carcinoma" (ISMC), pointing to an analogy to similar, high-risk HPV-driven malignancies recently described in the gynecologic (GYN) and genitourinary (GU) areas. Both tumors, despite their mucoepidermoid-like features had no connection to salivary glands and lacked the MAML2 translocation typical of salivary gland MEC, pointing to a mucosal/non-salivary gland origin. Using these two carcinomas as examples, we attempt to address questions related to: (a) the histological distinction between MEC, adenosquamous carcinoma, and ISMC, (b) similarities and differences between these histological entities in mucosal sites versus morphologically similar salivary gland tumors, and (c) the role of HPV in these tumors.

Emphysematous gastritis due to Sarcina ventriculi infection in a diabetic liver-kidney transplant recipient.

Emphysematous gastritis (EG) is a rare and potentially lethal process caused by invasive, gas-producing bacteria leading to inflammation and gas dissection of the stomach. The most common etiologic agents are Clostridium infections, but other organisms, including enterobacteria, staphylococcus, and fungi have also been identified. We report the first case of EG due to Sarcina ventriculi in a solid organ transplant recipient, who presented with epigastric pain and vomiting. The patient had a history of type 1 diabetes mellitus (DM) with recurrent episodes of ketoacidosis and systemic diabetic complications, including severe gastroparesis. CT scan studies demonstrated EG with venous air, and endoscopy showed severe gastritis and ulcerations. In the gastric biopsies, abundant Sarcina ventriculi were noted in areas of mucosal/submucosal necrosis. Antibiotic treatment was instituted at admission, and subsequent endoscopy demonstrated the disappearance of Sarcina, with some improvement of the gastric inflammation; however, the patient developed septic shock with multiorgan failure and expired. This case highlights the need to consider other infectious etiologies in transplant patients, in addition to the well-known opportunistic infections.

Emphysematous Gastritis in a Transplant Recipient With Clostridium ventriculi Infection.

Clostridium ventriculi is a rare infection in poorly controlled diabetic patients with a history of gastroparesis. We present the first documented case in a transplant recipient, who underwent a simultaneous liver kidney transplant. Computed tomography showed emphysematous gastritis, endoscopy revealed gastric necrosis, and microscopy confirmed the diagnosis. Operative intervention was high risk, given the previous liver transplant. Antibiotics and proton pump inhibitor treatment with repeat endoscopy at 4 days showed resolution of gastric necrosis and elimination of microscopic evidence of infection. Combination antibiotic and proton pump inhibitor therapy may be an effective treatment for this rare, life-threatening infection.

Emphysematous gastritis due to Sarcina ventriculi infection in a diabetic liver-kidney transplant recipient

Emphysematous gastritis (EG) is a rare and potentially lethal process caused by invasive, gas-producing bacteria leading to inflammation and gas dissection of the stomach. The most common etiologic agents are Clostridium infections, but other organisms, including enterobacteria, staphylococcus, and fungi have also been identified. We report the first case of EG due to Sarcina ventriculi in a solid organ transplant recipient, who presented with epigastric pain and vomiting. The patient had a history of type 1 diabetes mellitus (DM) with recurrent episodes of ketoacidosis and systemic diabetic complications, including severe gastroparesis. CT scan studies demonstrated EG with venous air, and endoscopy showed severe gastritis and ulcerations. In the gastric biopsies, abundant Sarcina ventriculi were noted in areas of mucosal/submucosal necrosis. Antibiotic treatment was instituted at admission, and subsequent endoscopy demonstrated the disappearance of Sarcina, with some improvement of the gastric inflammation; however, the patient developed septic shock with multiorgan failure and expired. This case highlights the need to consider other infectious etiologies in transplant patients, in addition to the well-known opportunistic infections.

Comparison of the Diagnostic Yield of EUS Needles for Liver Biopsy: Ex Vivo Study.

BACKGROUND AND AIMS: EUS-guided liver biopsy is an emerging method of liver tissue acquisition which is safe and had been shown to produce excellent histological yield. There is limited data comparing the diagnostic yield of different FNA needles. We aimed to compare the diagnostic performance of four commercially available 19-gauge FNA needles. METHODS: Four FNA needles and one percutaneous needle were used to perform liver biopsies on two human cadaveric livers: Cook Echotip Procore™, Olympus EZ Shot 2™, Boston Scientific Expect Slimline™, Covidien SharkCore™, and an 18-gauge percutaneous needle (TruCore™, Argon Medical Devices). Each needle obtained biopsies by three, six, and nine complete back-and-forth motions of the needle ("throw") with a fanning technique. The combined lengths of specimen fragments and the total number of complete portal tracts (CPT) were measured by a blinded pathologist. One-way analysis of variance (ANOVA) and Bonferroni correction were used for statistical analysis. RESULTS: A total of 52 liver biopsies were performed. The Covidien SharkCore needle had significantly greater number of CPT compared to other FNA needles. The number of "throws" did not impact the number of CPT significantly. There was no statistically significant difference in mean total specimen length between each FNA needle type. CONCLUSION: The Covidien SharkCore needle produced superior histological specimen by capturing more CPT, possibly due to its unique needle design.

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. RESULTS: The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. CONCLUSIONS: High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.

Rapid progression of a pregnancy-associated intra-abdominal desmoid tumor in the post-partum period: A case report.

INTRODUCTION: The clinical behavior of desmoid tumors can be unpredictable, particularly when they arise in the ante-partum or post-partum period. We present a case of an intra-abdominal desmoid tumor that was identified in the ante-partum period, progressed rapidly in the post-partum period, and was subsequently resected. PRESENTATION OF CASE: The patient is a 19 year-old female who was found to have a 12cm intra-abdominal mass on a fetal assessment ultrasound. The decision was made to observe the patient and monitor the mass for growth. However, the mass rapidly grew in the post-partum period. The patient was transferred to our institution after an exploratory laparotomy revealed a large intra-abdominal mass emanating from the small bowel mesentery. The 30cm×24cm×16cm mass was successfully resected with negative margins, and the pathologic diagnosis of desmoid tumor was confirmed. The patient had an uncomplicated post-operative course and was discharged on post-operative day 6. DISCUSSION: The majority of pregnancy-associated desmoid tumors are in the abdominal wall, arising from the rectus abdominus muscle or from previous Cesarean section scars. These tumors may spontaneously regress in the post-partum period and therefore, patients with these tumors are often observed. Close follow-up is important so that rapid tumor progression, which may lead to unresectability, can be identified and managed appropriately. CONCLUSION: A patient with a rare case of a giant pregnancy-associated, intra-abdominal desmoid tumor that rapidly progressed in the post-partum period and was successfully treated with surgical resection with negative margins.

Acute Hepatocellular Drug-Induced Liver Injury From Bupropion and Doxycycline.

The management and diagnosis of drug-induced liver injury (DILI) is often challenging, particularly when patients are taking multiple medications. We present a 29-year-old African American man who presented with jaundice and malaise after starting bupropion and doxycycline 2 weeks prior. He was found to have acute hepatocellular drug-induced liver injury with autoimmune features, and made a complete recovery with prednisone. Although bupropion and doxycycline are both known to cause liver toxicity, a closer inspection of the signature of liver injury and a review of prior related DILI cases assigns causality more to bupropion than doxycycline.

M1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice.

Cholinergic nervous system regulates liver injury. However, the role of M1 muscarinic receptors (M1R) in modulating chronic liver injury is uncertain. To address this gap in knowledge we treated M1R-deficient and WT mice with azoxymethane (AOM) for six weeks and assessed liver injury responses 14 weeks after the last dose of AOM. Compared to AOM-treated WT mice, M1R-deficient mice had attenuated liver nodularity, fibrosis and ductular proliferation, α-SMA staining, and expression of α1 collagen, Tgfß-R, Pdgf-R, Mmp-2, Timp-1 and Timp-2. In hepatocytes, these findings were associated with reductions of cleaved caspase-3 staining and Tnf-α expression. In response to AOM treatment, M1R-deficient mice mounted a vigorous anti-oxidant response by upregulating Gclc and Nqo1 expression, and attenuating peroxynitrite generation. M1R-deficient mouse livers had increased expression of Trail-R2, a promotor of stellate cell apoptosis; dual staining for TUNNEL and α-SMA revealed increased stellate cells apoptosis in livers from M1R-deficient mice compared to those from WT. Finally, pharmacological inhibition of M1R reduced H2O2-induced hepatocyte apoptosis in vitro. These results indicate that following liver injury, anti-oxidant response in M1R-deficient mice attenuates hepatocyte apoptosis and reduces stellate cell activation, thereby diminishing fibrosis. Therefore, targeting M1R expression and activation in chronic liver injury may provide therapeutic benefit.

Remission of Refractory Celiac Disease With Infliximab in a Pediatric Patient.

Refractory celiac disease (RCD) is a rare but life-threatening complication of celiac disease (CD), and only 1 pediatric case has been reported. We report a case of a 14-year-old girl with CD presenting with persistent symptoms and positive tissue celiac-specific antibodies despite a gluten-free diet. Push enteroscopy showed jejunal scalloping and partial villous atrophy on histology. She was diagnosed with RCD and treated with infliximab with subsequent complete serological and histological remission.

M1 muscarinic receptors modify oxidative stress response to acetaminophen-induced acute liver injury.

The role of muscarinic receptor subtypes in modulating acute liver injury is unknown. We detected M1 muscarinic receptor (M1R) expression in human and murine hepatocytes, and investigated the consequences of M1R deficiency on acute liver injury in vivo and inhibiting M1R activation on hepatocyte injury in vitro. Age-matched wild-type (WT) and M1R-deficient (Chrm1(-/-)) male mice were injected intraperitoneally with 200mg/kg acetaminophen (APAP) and euthanized 0, 2, 4, 16, 24, and 36h later. Biochemical and histological parameters indicated that liver injury peaked within 16h after APAP treatment and resolved by 24h. Compared to WT, M1R-deficient mice had reduced intrahepatic hemorrhage and hepatocyte necrosis, reflected by an attenuated rise in serum alanine aminotransferase levels. Livers of M1R-deficient mice showed reduced hepatocyte DNA fragmentation and attenuated expression of injury cytokines (Il-1α, Il-1ß, Il-6, and Fasl). In all mice hepatic glutathione levels decreased after APAP injection, but they recovered more quickly in M1R-deficient mice. During the course of APAP-induced liver injury in M1R-deficient compared to WT mice, hepatic Nrf-2, Gclc, and Nqo1 expressions increased and nitrotyrosine generation decreased. APAP metabolic pathways were not altered by M1R deficiency; expression of hepatic Cyp2e1, Cyp1a2, Cyp3a11, Cyp3a13, Car, and Pxr was similar in Chrm1(-/-) and WT mice. Finally, treatment of murine AML12 hepatocytes with a novel M1R antagonist, VU0255035, attenuated H2O2-induced oxidative stress, prevented GSH depletion, and enhanced viability. We conclude that M1R modify hepatocyte responses to oxidative stress and that targeting M1R has therapeutic potential for toxic liver injury.

Ectopic ureter presenting as anterior wall vaginal prolapse.

The differential diagnoses for anterior wall vaginal prolapse (AWVP) include cystocele, enterocele, urethral diverticulum, and Gartner duct cyst. We present a case of a patient with a known solitary right kidney (congenital absence of a left kidney) presenting with lower urinary tract symptoms, absence of urinary incontinence, and feeling of bulge in the vagina. Physical examination revealed grade II AWVP. Because congenital solitary kidney can be associated with other possible genitourinary abnormalities, a pelvic magnetic resonance imaging was obtained. Magnetic resonance imaging demonstrated a tubular structure spanning the left retroperitoneum to the region of the AWVP. Urodynamics revealed an obstructive voiding pattern during pressure-flow phase. The combination of transvaginal and transabdominal surgical excision of the tubular structure resolved the patient's lower urinary tract and prolapse symptoms. Anatomically, her AWVP was corrected. Histopathologic examination of the tubular structure revealed presence of urothelium lining the lumen of the tubular structure consistent with a ureter. This case represents the rare situation in which an ectopic ureter presented as an AWVP. However, patients with congenital solitary kidney presenting with vaginal prolapse should raise the suspicion for other associated genitourinary anomalies, whether these anomalies are related to the prolapse or not. Cross-sectional imaging should be performed in these situations to delineate precise anatomy.

Human airway epithelia express catalytically active NEU3 sialidase.

Sialic acids on glycoconjugates play a pivotal role in many biological processes. In the airways, sialylated glycoproteins and glycolipids are strategically positioned on the plasma membranes of epithelia to regulate receptor-ligand, cell-cell, and host-pathogen interactions at the molecular level. We now demonstrate, for the first time, sialidase activity for ganglioside substrates in human airway epithelia. Of the four known mammalian sialidases, NEU3 has a substrate preference for gangliosides and is expressed at mRNA and protein levels at comparable abundance in epithelia derived from human trachea, bronchi, small airways, and alveoli. In small airway and alveolar epithelia, NEU3 protein was immunolocalized to the plasma membrane, cytosolic, and nuclear subcellular fractions. Small interfering RNA-induced silencing of NEU3 expression diminished sialidase activity for a ganglioside substrate by >70%. NEU3 immunostaining of intact human lung tissue could be localized to the superficial epithelia, including the ciliated brush border, as well as to nuclei. However, NEU3 was reduced in subepithelial tissues. These results indicate that human airway epithelia express catalytically active NEU3 sialidase.