Patients undergoing allogeneic stem cell transplant are at significant risk of infections due to the immunosuppression resulting from leukopenia as well as immunosuppressive agents for graft versus host disease prophylaxis or management. Organisms that normally do not result in significant clinical manifestations can cause potentially lethal outcomes in infected allogeneic stem cell transplant patients. Diarrhea resulting from infectious etiology continues to remain a significant complication associated with allogeneic stem cell transplant. Norovirus gastroenteritis is a well described phenomenon in both pediatric as well as adult allogeneic hematopoietic stem cell transplant recipients. There is no definite treatment available for managing this complication and supportive care and withdrawal of immunosuppression continues to remain the mainstay. We report the case of a 68-year-old Caucasian female who underwent a haplo-identical stem cell transplant for high-risk acute myeloid leukemia with FLT3 mutation. The patient developed diarrhea on day+4 and her stool tested positive for Clostridium difficile. Even though she initially responded to appropriate treatment for Clostridium difficile, her diarrhea recurred. Repeat testing for infectious etiology revealed the presence of norovirus while Clostridium difficile was no longer detected. The patient was treated with oral nitazoxanide 500 mg BID for 10 days with significant clinical improvement in her stool volume and frequency as well as consistency. However, she continued to shed the virus even after clinical improvement. Nitazoxanide was developed in 1970 and was initially perceived to be an anti-protozoal agent. An increasing amount of pre-clinical and clinical research has indicated that it is active against a broad variety of organisms including anaerobic gram-positive and gram-negative bacteria, mycobacterium tuberculosis, respiratory viruses as well as rotavirus and norovirus. While there is literature supporting the use of nitazoxanide in other immunosuppressed patients such as HIV infected and solid organ transplant patients, information regarding the safety and efficacy of nitazoxanide for treating norovirus in adult allogeneic stem cell transplant patients is very limited (one case report identified in Pubmed). Our case demonstrates that even in early post-transplant setting, nitazoxanide effectively controlled norovirus gastroenteritis without compromising graft function. The utility of Nitazoxanide in viral gastroenteritis in allogeneic hematopoietic transplant patients should be explored further in prospective trials.Tabled 1Pubmed search using the terms "Nitazoxanide" AND one of the following# of Items in search resultsRelevant to clinical use of Nitazoxanide for Norovirus in Hematopoietic Stem Cell transplantHematopoietic transplant31Stem cell transplant51Norovirus101 Open table in a new tab
Upper respiratory infections can be complicated by acute bacterial sinusitis in pediatric patients, and usually resolve with antibiotic therapy (DeMuri and Wald, 2011). However, intracranial complications such as: epidural abscess, meningitis and more rarely cerebral sinus venous thrombosis (CSVT) can occur (Germiller et al., 2006). We report an unusual case of sinusitis complicated by an epidural abscess and later a CSVT in a young previously healthy patient.A 12-year-old female presented to the emergency department with a 9-day history of headaches and a 3-day history of fevers, rigors, nasal congestion and nonproductive cough. She later tested positive for Covid-19. CT and MRI showed extensive paranasal sinus disease and a right frontal epidural collection. MRV showed no sinovenous thrombosis. Washout and burr hole drainage alongside endoscopic sinus surgery was completed and post-op imaging showed evacuation of the epidural abscess with a small residual collection. Six days after the procedure, she experienced worsening headaches and MRV showed a nonocclusive thrombus in the superior sagittal sinus, which was treated with anticoagulation therapy. Upon follow-up, the patient showed improvement of the sinusitis, abscess and thrombus.This specific case encourages clinicians to be aware of complications, though rare, and to diagnose and treat sinusitis cases quickly. It is also important to be aware of any risk factors for thrombus formation, including an inflammatory and hypercoagulable state. In the patient's case, it was perceived that the CSVT was provoked due to the patient's Covid-19 infection, abscess, and sinus disease.
Nivolumab, a programmed death 1 (PD-1) blocking antibody, is approved in relapsed or refractory Hodgkin's lymphoma (HL) and exerts its effect by blocking a negative regulator of T-cell activation thus enhancing immune effector function against lymphoma. To our knowledge, Nivolumab has never been evaluated after allogeneic stem cell transplantation in HLA-mismatched setting. Here we describe a 23-year-old male with Classical Hodgkin's Lymphoma Nodular Sclerosing type who relapsed after autologous stem cell transplantation. He was treated with Brentuximab and achieved a complete response prior to undergoing allogenic stem cell transplantation. The conditioning was reduced intensity Fludarabine and Busulfan (Flu/Bu2) and graft source was bone marrow from an HLA-A antigen mismatched unrelated donor. The Graft versus Host Disease (GVHD) prophylaxis was thymoglobulin, Bortezomib, Tacrolimus, and Methotrexate. The patient had an uneventful post-transplant course with no GVHD but unfortunately around day+100 he presented with night sweats and pruritus. A CT Chest/Abdomen subsequently showed small volume lymphadenopathy (LAD) in the pretracheal, supraclavicular and para-aortic region. The biopsy of para-aortic LN confirmed relapsed disease. Immunosuppression was subsequently discontinued but a repeat positron emission tomography (PET/CT) scan showed progressive disease. He was treated with five cycles of Brentuximab, without significant benefit. The patient declined further therapy and donor lymphocyte infusion and was lost to follow up for eight months. The patient sought treatment at a different facility and received a single cycle of Bendamustine but returned to our facility with abdominal pain and palpable LAD. A PET scan confirmed further progression of his disease. We began treatment with Nivolumab but the initial dose was cut by 50% to 1.5 mg/Kg due to concerns for GVHD in the mismatched setting. After two cycles of reduced dose Nivolumab, and no obvious signs of GVHD, the Nivolumab dose was increased to standard 3 mg/kg. A repeat PET/CT scan following 2 cycles showed significant improvement in LAD. The patient has currently completed 4 cycles of Nivolumab without any significant GVHD. In conclusion, treatment with anti-PD1 antibody checkpoint inhibitor, Nivolumab, appears to be effective and safe in Hodgkin's patients without GVHD following mismatched allogeneic stem cell transplantation.
Rearing social animals like pigs in isolation from conspecifics can have consequences on behaviour and physiology. The aim of this experiment was to determine whether rearing conditions affect body posture. We adapted a method for quantitative evaluation of posture based on geometric morphometrics, developed in horses, for pigs and applied it in different conditions. Forty-eight 75-day-old females were reared either alone in 2.25 m2 pens (IH, N = 24 animals and 4 groups) or in groups of four in 4.64 m2 pens (GH, N = 24) for two weeks. They were habituated to human handling (stroking, speaking) and marking on their backs every day, and tested individually once a day for 10 min in a corridor outside the home pen during the two subsequent weeks. We observed their behaviour and posture during the first exposure to the test (novelty), and the fourth and fifth (after habituation). On the sixth and seventh tests, a familiar stockperson was present in the corridor (human presence). Before each test, the animals were marked with seven landmarks along their length, corresponding to their anatomical points and were easily located. An experimenter took pictures of the animals walking along the corridor, and these pictures were transferred to Tps software for analysis.GH animals were more often active in the rearing pen than IH (median (IQ) 15% of observations [12–20%] versus 2% [0–13%]; P < 0.05). All animals except one IH initiated contact with the handler during the last sessions of handling (Fisher's exact test, ns). Principal Component Analyses revealed significant effects of rearing and testing conditions on pigs’ behaviour and posture. Novelty led to fewer vocalisations and more exploration for IH than GH animals (P < 0.05), but there were no differences between treatments after habituation to the testing situation. The backs of IH animals were more rounded than those of GH (P < 0.05; dimension 1 of PCA), independently of the test condition. Human presence had no effect on posture.In conclusion, the method based on geometric morphometrics that we developed to study pig posture detected variations in walking posture in pigs associated with rearing conditions. Postures might reflect affective states in pigs, as shown in other species, but further studies are needed to verify this.
Chronic GVHD can have a significant impact on the quality of life and is an important consideration while deciding for allogeneic stem cell transplant. Beyond the 1st line use of corticosteroids, there is no established order of treatment options. Ruxolitinib is a first-in-class JAK1/JAK2 inhibitor that was approved for management of acute GVHD. Here, we present our experience using ruxolitinib for chronic GVHD.We identified 30 patients at our center who have been treated with ruxolitinib for chronic GVHD. A retrospective chart review was conducted to gather data. Chronic GVHD was graded in individual organ systems according to the NIH severity scoring. NIH criteria for global severity and response assessment were not used. While valuable for clinical trials, these are challenging to use in daily practice. We considered each involved organ in a patient as an 'event' (total 143 'events' in 30 patients.) Severity score before and after starting ruxolitinib for each event was compared. Outcomes were classified in to 4 groups – Improvement, Stable, Worsening and New Onset (after start of ruxolitinib.) Using this system, 53 (37%) events showed an improvement, 70 (49%) were stable, 6 (4%) had worsening while 14 (10%) new onset events occurred after starting ruxolitinib.Majority of the patients had been transplanted for MDS/AML (23/30) from MRD (14/30) or MUD (13/30) using PBSC (28/30). Dose reduction was needed in 8/30 patients; 6 due to cytopenias and 1 each for drug-interaction and rectal bleeding. We also reviewed prior, concomitant and additional therapies used. Effects of chronic GVHD on lung are often irreversible. Interestingly, two of our lung GVHD patients were able to come off continuous oxygen.This observation suggests ruxolitinib as a safe and effective option for treatment of chronic GVHD even in heavily pretreated patients. Chronic GVHD can have a significant impact on the quality of life and is an important consideration while deciding for allogeneic stem cell transplant. Beyond the 1st line use of corticosteroids, there is no established order of treatment options. Ruxolitinib is a first-in-class JAK1/JAK2 inhibitor that was approved for management of acute GVHD. Here, we present our experience using ruxolitinib for chronic GVHD. We identified 30 patients at our center who have been treated with ruxolitinib for chronic GVHD. A retrospective chart review was conducted to gather data. Chronic GVHD was graded in individual organ systems according to the NIH severity scoring. NIH criteria for global severity and response assessment were not used. While valuable for clinical trials, these are challenging to use in daily practice. We considered each involved organ in a patient as an 'event' (total 143 'events' in 30 patients.) Severity score before and after starting ruxolitinib for each event was compared. Outcomes were classified in to 4 groups – Improvement, Stable, Worsening and New Onset (after start of ruxolitinib.) Using this system, 53 (37%) events showed an improvement, 70 (49%) were stable, 6 (4%) had worsening while 14 (10%) new onset events occurred after starting ruxolitinib. Majority of the patients had been transplanted for MDS/AML (23/30) from MRD (14/30) or MUD (13/30) using PBSC (28/30). Dose reduction was needed in 8/30 patients; 6 due to cytopenias and 1 each for drug-interaction and rectal bleeding. We also reviewed prior, concomitant and additional therapies used. Effects of chronic GVHD on lung are often irreversible. Interestingly, two of our lung GVHD patients were able to come off continuous oxygen. This observation suggests ruxolitinib as a safe and effective option for treatment of chronic GVHD even in heavily pretreated patients. Tabled 1 Open table in a new tab
