bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous stem cell transplantation vs bortezomib based chemotheraphy for the first‐line treatment of systemic light chain amyloidosis in the UK
Authors: Sharpley Faye A. , Manwani Richa , Petrie Aviva , Mahmood Shameem , Sachchithanantham Sajitha , Lachmann Helen J. , Martinez De Azcona Naharro Ana , Gillmore Julian D. , Whelan Carol J. , Fontana Marianna , Cohen Oliver , Hawkins Philip N. , Wechalekar Ashutosh D.
Published: January 2021

Objectives

The benefit of autologous stem cell transplantation (ASCT) in the treatment of light chain (AL) amyloidosis requires re‐evaluation in the modern era. This retrospective case‐matched study compares ASCT to bortezomib for the treatment of patients with AL amyloidosis.

Methods

Newly diagnosed patients with AL amyloidosis treated with ASCT or bortezomib between 2001 and 2018 were identified. Patients were excluded if the time from diagnosis to treatment exceeded 12 months. Patients were matched on a 1:1 basis, using a propensity‐matched scoring approach.

Results

A total of 136 propensity score‐matched patients were included (ASCT n = 68, bortezomib n = 68). There was no significant difference in overall survival at two years (P = .908, HR: 0.95, CI: 0.41‐2.20). For ASCT vs bortezomib: overall haematological response rate at 6 months was 90.6% vs 92.5%; organ response at 12 months: cardiac (70.0% vs 54%, P > .999), renal (74% vs 24%, P = .463) liver (21% vs 22%, P = .048); median progression‐free survival (50 vs 42 months P = .058, HR: 0.61, CI: 0.37‐1.02) and time to next treatment (68 vs 45 months, P = .145, HR: 0.61, CI: 0.31‐1.19). More patients required treatment in the bortezomib group compared to ASCT group at 24 months (41 vs 23, Chi‐squared P = .004) and 48 months (57 vs 41, Chi‐squared P = .004).

Conclusions

This small retrospective study suggests that there is no clear survival advantage of ASCT over bortezomib therapy. A prospective randomised controlled trial evaluating ASCT in AL amyloidosis is critically needed.
Nest‐site selection in a neotropical arachnid with exclusive male care: Proximate cues and adaptive meaning
Authors: Rojas Andrés , Muniz Danilo G. , Solano‐Brenes Diego , Machado Glauco
Published: January 2021

Nest‐site selection is a crucial decision made by parents because inadequate sites may expose the offspring and the parent to harsh abiotic and biotic conditions. Although nest‐site selection has been reported for some species of arthropods, the proximate cues used by parents to select the nest site and the adaptive meaning of nest‐site selection are still poorly understood. We investigated nest‐site selection in the harvestman Quindina limbata, in which males build mud nests on the surface of fallen logs and perform parental care. This species inhabits tropical forests where rainfall destroys nearly 50% of the nests, representing an important selective force shaping nest‐site selection. We followed 139 nests and recorded the position (angle) where these nests were located on the fallen log surface. Males showed a complex pattern of nest‐site selection that responded to three proximate cues: the direct impact of raindrops on the upper half of the fallen log, the drag force caused by flowing water on the laterals of the fallen log, and water saturation on the lowest part of the fallen log. These selective pressures created a bimodal pattern of nest distribution on the lower half of the fallen logs. The peaks of this distribution occurred in places where nests are protected from the direct impact of raindrops, the drag force caused by flowing water is not high, and the risk of nest flooding is low. The possible adaptive meaning of nest‐site selection is to minimize the risk of nest destruction, which imposes energetic costs to males that need to build another nest. Nest‐site selection may also minimize reproductive costs because males with damaged nests show decreased attractiveness to females. Finally, nest‐site selection may increase offspring fitness minimizing the risk of egg mortality associated with nest destruction and anoxia when nests are flooded.
The role of prolines and glycine in the transmembrane domain of LAT
Authors: Glatzová Daniela , Mavila Harsha , Saija Maria Chiara , Chum Tomáš , Cwiklik Lukasz , Brdička Tomáš , Cebecauer Marek
Published: January 2021

Linker for activation in T cells (LAT) is a critical regulator of T‐cell development and function. It organises signalling events at the plasma membrane. However, the mechanism, which controls LAT localisation at the plasma membrane, is not fully understood. Here, we studied the impact of helix‐breaking amino acids, two prolines and one glycine, in the transmembrane segment on localisation and function of LAT. Using in silico analysis, confocal and super‐resolution imaging and flow cytometry, we demonstrate that central proline residue destabilises transmembrane helix by inducing a kink. The helical structure and dynamics are further regulated by glycine and another proline residue in the luminal part of LAT transmembrane domain. Replacement of these residues with aliphatic amino acids reduces LAT dependence on palmitoylation for sorting to the plasma membrane. However, surface expression of these mutants is not sufficient to recover function of nonpalmitoylated LAT in stimulated T cells. These data indicate that geometry and dynamics of LAT transmembrane segment regulate its localisation and function in immune cells.
Microglial changes in healthy mice retina in an early aging stage
Authors: Fernández‐Albarral José A. , Salobrar‐Garcia Elena , López‐Cuenca Inés , Rojas Lozano María Pilar , José Salazar Corral Juan , De Hoz Rosa , Aviles‐Trigueros Marcelino , Vidal‐Sanz Manuel , Ramirez Jose Manuel , Ramírez Ana I.
Published: January 2021

Purpose

To quantify different morphological signs of microglial cells activation, as well as to analyze the P2RY12, MHC‐II and CD68 expression in 15‐month old mice , an early stage of aging (aged naïve) in comparison with a young adult mice (young naïve).

Methods

Young naïve (n = 6) and aged naïve (n = 6) mice were analyzed. Retinal whole‐mounts were immunolabeled with: 1) anti Iba‐1 to quantify: i) Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ ganglion cell layer (NFL‐GCL) iii) cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; iv) arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL; number of vertical processes of Iba‐1+ cells (VPIbac) beetween the OS and OPL. 2) anti‐P2RY12 to identify resident microglia, anti‐CD68 and anti‐MHC‐II as a microglial activation marker.

Results

In aged naïve with respect to young naïve the quantitative analysis showed: i) a non‐significant increase in the Ibacn in OS; ii) a non‐significant decrease in the AAIbac in OPL; iii) a significant increase in the CbIbac in OPL, IPL and NFL‐GCL and iv) a significant increase in the VPIbac. When we analyzed the expression of P2RY12, CD68 and MHC‐II we observed: i) in young naïve all Iba‐1+ cells were P2RY12+, except perivascular and dendritic cells, but in the aged naïve some cells were Iba‐1+/P2RY12‐; ii) in aged naïve numerous amoeboid‐like CD68+ cells were found while in the young naïve the expression of CD68 practically was absent, and iii) in both young naïve and aged naïve no expression of MHC‐II was observed.

Conclusions

In 15‐month‐old mice, morphological changes and in the expression of P2RY12, CD68 and MHC‐II occurs in the microglial cells compared to young adult mice. These signs show a non‐pathological state of microglial activation that could influence of retinal age‐related disorders.
Long‐term Graft Survival and Visual Outcome of Deep Anterior lamellar keratoplasty versus penetrating keratoplasty for keratoconus: A minimum of 10 years follow‐up
Authors: Almazyad Enmar , Alosaily Abdullah , Ahmad Abeer , Al‐Swailem Samar
Published: January 2021

Purpose

To compare long‐term visual outcome and graft survival between Deep Anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) for keratoconus (KC), with a minimum of ten years follow‐up.

Methods

Retrospective, comparative cohort study of 191 KC eyes who underwent DALK and PK between January 2000 and October 2006, at a largest tertiary eye hospital in the country. Baseline and postoperative outcomes included: best‐corrected visual acuity (BCVA), spherical equivalent (SE), keratometric power, and keratometric astigmatism. Difference in overall effect and effect at each time point were presented. Graft survival was analyzed with use of the Kaplan ‐Meier survival method.

Results

97 (50.8%) eyes underwent PK and 94 (49.2%) eyes underwent DALK. mean follow‐up in PK & DALK groups were 13.45±2.7 years and 12.18±1.9 years, respectively. Post‐operative Mean BCVA (LogMar) was significantly worse in DALK (0.49 ± 0.26) in comparison to PK (0.40 ± 0.2) at 3 months whereas BCVA was significantly better in DALK (0.23 ± 0.18) in comparison to PK (0.37 ± 0.63) at the last follow‐up. However, the overall effect of BCVA for both groups was insignificant. The overall effect of SE and keratometric power were insignificant. More complications were reported in PK (69%) group versus DALK (31%). At last follow‐up, 15 grafts failed, 9 were PK and 6 were DALK. Graft rejection was the most common reported cause of failure in both groups (PK 73%, DALK 50%). There was no overall significant difference between PK and DALK in time to graft failure (p = 0.59).

Conclusions

Long‐term follow‐up of PK and DALK for KC showed similar overall graft survival and no significant difference in mean BCVA overall effect, indicating that both keratoplasties can offer long‐term satisfactory visual outcomes with less rejection and less overall post‐operative complications in DALK.
Causes of low vision in a Greek population
Authors: Almpanidou Stavroula , Almaliotis Diamantis , Karamitopoulos Leonidas , Topouzis Fotios , Labiris Georgios , Karampatakis Vasileios
Published: January 2021

Purpose

Low vision (LV) is one of the major causes affecting detrimentally the quality of life of individuals. There are various underlying ocular pathologies resulting in LV. The purpose of this study is to determine the prevalence of the main causes of low vision in a population attended a university outpatient unit in Greece.

Methods

The records of all patients within a timeframe of about 18 months period were retrospectively reviewed. In this study, individuals with best‐corrected visual acuity (BCVA) of 3/60 to <6/18 were characterized as having LV, according to the World Health Organization (WHO) definition of LV.

Results

Two hundred thirty‐six LV patients were included—114 (48.3%) were males and 122 (51.7%) females. The age of patients ranged from ten to ninety‐nine, with a mean age of 70.9 ± 18.9 years. BCVA ranged from 1.32 logMAR to 0.33 logMAR, with a mean VA of 0.7152 ± 0.3146 logMAR in the better eye. The distribution of LV causes in this population was the following: Age‐related macular degeneration (AMD) accounting for 50.0% of the cases (118/236), diabetic retinopathy (DR) 19.9% (47/236) and glaucoma 7.2% (17/236). Other causes of LV included retinitis pigmentosa in a percentage of 5.3% and other hereditary retinal diseases (3%), previous retinal detachment (2.5%), other maculopathies (2.1%) and various other ocular diseases (9.7%). Out of 118 patients with AMD, 75 (64.1%) had the dry form and 42 (35.9%) had the wet form of the disease and among patients with diabetic retinopathy as underlying cause of LV, 31 (68.9%) had the proliferative and 14 (31.1%) had the non‐proliferative form of the disease.

Conclusions

Age‐related macular degeneration, diabetic retinopathy and glaucoma constituted the three main causes of low vision in the study population, followed by other ocular diseases.
Comment on: Virtual funerals: A feasible and safer option during the COVID‐19 pandemic
Authors: Sherman Fredrick T.
Published: January 2021

See the Reply by Freeman et al.
Italian expert‐based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e‐Delphi consensus
Authors: Grandi Vieri , Baldo Antonello , Berti Emilio , Quaglino Pietro , Rupoli Serena , Alaibac Mauro , Alberti‐Violetti Silvia , Amerio Paolo , Brazzelli Valeria , Bruni Pier Luigi , Calzavara‐Pinton Piergiacomo , Parodi Aurora , Cozzani Emanuele , Burlando Martina , Fargnoli Maria Concetta , Gambini Daniele , Iacovelli Paolo , Pacifico Alessia , Longo Caterina , Monfrecola Giuseppe , Motolese Alberico , Mozzicafreddo Giorgio , Cota Carlo , Pigatto Paolo , Pileri Alessandro , Savoia Paola , Simonacci Marco , Venturini Marina , Offidani Annamaria , Molinelli Elisa , Pellegrino Michele , Trovato Emanuele , Piccinno Roberta , Lawrence Karl , Pimpinelli Nicola
Published: January 2021

Background

Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule.

Aims

The primary aim of this study was to establish the first structured, expert‐based consensus regarding the indications and technical schedules of NB‐UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item.

Materials & Methods

E‐delphi study. Item‐specific expert consensus was defined as the number of “Totally Agree” results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic.

Results

Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7).

Conclusions

Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB‐UVB and PUVA in MF.
A long‐term in vitro culture of bovine epithelial cells on collagen rafts
Authors: Peña‐Zanoni Milagros , García Daniela Celeste , Roldán‐Olarte Mariela , Valdecantos Pablo Alberto
Published: January 2021

In the present work, we established and characterized a 3D functional polarized primary bovine oviduct epithelial cells (BOECs) culture on free‐floating type I collagen hydrogels (rafts) at an air‐liquid interface (ALI). Intercellular junctions, ultrastructural cellular morphology and the expression of the OVGP1 closely recapitulated those of the in vivo epithelium lining. These morphological and physiological epithelial cell features were maintained under standard DMEM/F12 with 10% foetal bovine serum culture medium for at least 28 days of ALI culture. The versatility of the BOECs raft cultures should allow testing of toxicity compounds, in vitro evaluation of physiological or pathological oviductal states, and the study of epithelial‐mesenchymal interactions that are critical for the maintenance of oviductal homeostasis.
Modeling of a Fractional Order Element Based on Bacterial Cellulose and Ionic Liquids
Authors: Caponetto R. , Graziani S. , Murgano E. , Trigona C. , Pollicino A. , Di Pasquale G.
Published: January 2021

In this paper, a novel fractional-order element (FOE) is modeled in a wide frequency range. The FOE is based on a green biopolymer, i.e., bacterial cellulose (BC), infused with ionic liquids (ILs). The modeling is performed in the frequency domain and a lumped-circuit model is proposed. The model is an evolution with respect to a simpler one already introduced by the authors, for a narrower frequency range. Results show that ILs generate a quite complex frequency domain behavior, which can be described in the framework of FOEs. Furthermore, results on the time stability of the device under investigation are given.
Predictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosa
Authors: Mehla Jitender , Malloci Giuliano , Mansbach Rachael , López Cesar A. , Tsivkovski Ruslan , Haynes Keith , Leus Inga V. , Grindstaff Sally B. , Cascella Robert H. , D’Cunha Napoleon , Herndon Liam , Hengartner Nicolas W. , Margiotta Enrico , Atzori Alessio , Vargiu Attilio V. , Manrique Pedro D. , Walker John K. , Lomovskaya Olga , Ruggerone Paolo , Gnanakaran S. , Rybenkov Valentin V. , Zgurskaya Helen I.
Published: January 2021

Efflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular and physicochemical interactions defining the interface between compounds and efflux pumps remain poorly understood. We identified properties that correlate with efflux avoidance and inhibition, are predictive of similar features in structurally diverse compounds, and allow researchers to distinguish between efflux substrates, inhibitors, and avoiders in
P. aeruginosa
.
Stenoparib, an Inhibitor of Cellular Poly(ADP-Ribose) Polymerase, Blocks Replication of the SARS-CoV-2 and HCoV-NL63 Human Coronaviruses
In Vitro
Authors: Stone Nathan E. , Jaramillo Sierra A. , Jones Ashley N. , Vazquez Adam J. , Martz Madison , Versluis Lora M. , Raniere Marlee O. , Nunnally Haley E. , Zarn Katherine E. , Nottingham Roxanne , Ng Ken R. , Sahl Jason W. , Wagner David M. , Knudsen Steen , Settles Erik W. , Keim Paul , French Christopher T.
Published: January 2021

New therapeutics are urgently needed in the fight against COVID-19. Repurposing drugs that are either already approved for human use or are in advanced stages of the approval process can facilitate more rapid advances toward this goal.
Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients
Authors: Fishbein Skye R. S. , Hink Tiffany , Reske Kimberly A. , Cass Candice , Struttmann Emily , Iqbal Zainab Hassan , Seiler Sondra , Kwon Jennie H. , Burnham Carey-Ann D. , Dantas Gautam , Dubberke Erik R.
Published: January 2021

A gold standard diagnostic for
Clostridioides difficile
infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay.
Olfactory neurocytoma as a unique cause of chronic SIADH
Authors: Farwana Mohammad , Tornari Chrysostomos , Sandison Ann , Surda Pavol
Published: January 2021

A 32-year-old man was found to have a nasal mass on DOTATATE positron emission tomography (PET) scan to investigate the cause of his syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient presented 6 years earlier with malignant hypertension followed by a second emergency admission for hyponatraemia. Multiple scans and blood tests over 6 years yielded no cause for his SIADH. Nasendoscopy was unremarkable. A PET scan prompted endoscopic sinus surgery which resulted in the resection of a mass in the anterior hiatus semilunaris. The histological findings were fitting with a diagnosis of a neurocytic-type tumour favouring an olfactory neurocytoma. Following resection, the patient remains well and is cured of his SIADH. An olfactory neurocytoma although rare should be considered as a benign differential for a mass in the nasal space. This case demonstrates how an olfactory neurocytoma can present as a cause of SIADH.
Management of a complete hydatidiform mole with a coexisting live fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease: learning points
Authors: Mok Zhun Wei , Merchant Khurshid , Yip Swee Lin
Published: January 2021

A 34-year-old patient had her first trimester Down syndrome scan followed by serial ultrasound scans which showed a single intrauterine pregnancy with multiple cystic areas in the anterior placenta. She presented in preterm labour with a breech presentation at 32 weeks and underwent an emergency caesarean section. She delivered a male infant weighing 1750 g. The placental histopathology showed a complete hyatidiform mole. At 4 weeks postpartum, beta-human chorionic gonadotrophin (Bhcg) levels rose from 460 to 836 mIU/mL over 1 week. Metastatic workup revealed prominent pelvic nodes and pulmonary nodules in both lungs. This was discussed at the Multi-Disciplinary Tumour Board and single-agent intramuscular methotrexate was recommended. After chemotherapy, she achieved Bhcg normalisation after three cycles. This case highlights the importance of clinical vigilance even in low-risk patients. Unexpected findings on ultrasound should involve multidisciplinary input with radiology colleagues. A high index of suspicion for gestational trophoblastic disease and close follow-up is imperative.
Social taboos: a formidable challenge in cancer care
Authors: Kaul Pallvi , Kumar Rahul , Singh Mahendra Pal , Garg Pankaj Kumar
Published: January 2021

Taboo surrounding cancer has continued to be a stubborn and refractory public health issue especially in South Asian countries. Disparities in cancer care remain ubiquitous. Differences in the manner in which cancer is perceived, addressed, and treated might partly be a result of varying cultural influences. This case report highlights the clinical course of a female patient with neurofibromatosis who later developed a large facial malignant peripheral nerve sheath tumour. The case particularly addresses the catastrophic impact of the ‘cancer-related social taboos’ on various dimensions of cancer care ranging from primary and secondary prevention to definitive management. The financial issues in low-income to medium-income groups as potential deterrents to optimum treatment have also been highlighted. Approach to the common challenges faced by an oncologist practising in a society plagued by misconceptions about health and disease and potential remedial measures to debunk these myths have also been discussed.
Elastic intramedullary nail treatment of adolescent perihardware radius and ulna refracture
Authors: Griffin Carah M , Somerson Jeremy S
Published: January 2021

A 13-year-old girl presented to the clinic with a midshaft refracture of both forearm bones adjacent to the site of a prior forearm fracture that had been treated with plating. She was treated with hardware removal and placement of elastic intramedullary nails. Flexible intramedullary nailing can be successful for a skeletally mature adolescent in treatment of refracture surrounding plate fixation of a midshaft forearm fracture. This technique allows for additional protection of the entire length of the affected bones, while avoiding the extensive dissection needed for extended plating.
Giant fibroepithelial vulvar polyp in a pregnant woman
Authors: Smet Carolina , Gomes Tatiana Gigante , Silva Lurdes , Matias Júlio
Published: January 2021

Fibroepithelial polyps are benign lesions that may appear in the vulvovaginal region. They usually occur in women of reproductive age and tend to grow up to 5 cm, but there are some rare cases in which they grow up to 20 cm. We report a case of a 22-year-old woman in the third trimester of her first pregnancy with spontaneous bleeding from a pedunculated mass measuring 15 cm in the widest diameter on the right side of the vulva. Features of this case are discussed as well as its implications, especially regarding the decision of labour. Due to the big size of the mass and its propensity to bleed, we decided to perform an elective caesarean section as well as its excision.
Multidisciplinary management of patients with pubic osteomyelitis, a rare but serious complication after surgery and radiation therapy for advanced gynaecological cancer
Authors: Haveman Ilse , van Altena Anne M , Verschuren Charlotte PA , Aarts Johanna WM
Published: January 2021

Pubic osteomyelitis is a rare and often late-onset complication of radiation therapy and surgery for vulvar and vaginal carcinoma. It typically presents with vulvar pain, fever, vaginal discharge and/or gait disorders. Pubic osteomyelitis is often accompanied by fistulas or wound dehiscence in the pelvic area. Its accurate diagnosis and treatment are challenging and require a multidisciplinary team effort. In our patients, multiple combined surgical procedures, long-term antibiotic treatment and days to weeks of hospital admission were necessary to treat pubic osteomyelitis. We emphasise the importance of timely and adequate diagnosis and multidisciplinary approach resulting in a course of treatment that is as effective as possible, limiting the impact on quality of life, which is generally high in this group of patients.
Rare case of angiofibroma presenting as perineal hernia
Authors: Kumari Ruchika , Tandup Cherring , Agarwal Ambuj , Chowdhury Anish
Published: January 2021

Angiofibroma is a benign soft tissue tumour presenting as a gradually progressive swelling in the vulvovaginal area in women and in the inguinoscrotal region in men. Being a rare tumour, there are only a few case reports in the literature, and among them, presentation as perineal herniation is very rare. En bloc resection of angiofibroma either via laparoscopic or open approach is the choice of treatment to avoid recurrence. Detailed pathological examination and immunohistochemistry workup are imperative to distinguish it from various mesenchymal tumours. Perineal hernia is itself rare and may occur spontaneously or following abdominoperineal resection, sacrectomy or pelvic exenteration. Surgical repair via open transabdominal and transperineal approaches has been described. Here, we report a case of a young woman who presented with spontaneous reducible perineal hernia with a soft tissue tumour as its content, which on histopathological investigation was found to be an angiofibroma.
Adult-onset Woakes’ syndrome: a rare entity
Authors: Salvador Pedro , Moreira da Silva Francisco , Fonseca Rui
Published: January 2021

Woakes’ syndrome (WS) is a rare entity, defined as severe recalcitrant nasal polyposis with consecutive deformity of the nasal pyramid. WS occurs mainly in childhood and its aetiology remains unclear. We report a case of a 68-year old woman, with aspirin-exacerbated respiratory disease, who presented with recurrent nasal polyposis and progressive broadening of the nasal dorsum. CT scan revealed extensive bilateral nasal polyposis and diffuse osteitis, with anterior ethmoidal calcified lesions. The patient underwent revision endoscopic sinus surgery and nasal pyramid deformity was successfully managed without osteotomies.
Case of a chronic ectopic pregnancy misdiagnosed as pelvic inflammatory disease
Authors: Sekar Hashviniya , Divakova Olga , Alan Tanya , Premetis Gregory
Published: January 2021

The definition of a chronic ectopic pregnancy (CEP) is poorly defined in the literature and making a timely diagnosis can be incredibly challenging. This is primarily due to its broad range of clinical presentations and conflicting biochemical and sonographic results. Often, CEPs are mistaken for ovarian malignancies, pelvic inflammatory disease (PID), uterine fibroids or endometriosis, therefore, leading to a delayed diagnosis. We present a case report of a woman who was initially misdiagnosed with PID and then later preoperatively diagnosed with a CEP. This case particularly highlights the diagnostic dilemma posed by CEPs and raises awareness of the key clinical symptoms, biochemical and sonographic investigations which in combination can contribute towards making a timely preoperative diagnosis.
Infective endocarditis as a complication of longstanding ventriculoatrial (VA) shunt: the importance of suspicion and early investigation in patients with VA shunt and pyrexia of unknown origin
Authors: Sun Rosa , Warwick Richard , Harrisson Stuart , Bandla Nageswar
Published: January 2021

Ventriculoatrial (VA) shunts are a method of cerebrospinal fluid diversion, which nowadays are infrequently seen in medical practice. Infective endocarditis (IE) can occur as rare complications of VA shunts, through the introduction of a foreign body close to the tricuspid valve. We report a case of infective endocarditis, that is, in a patient with VA shunt for congenital hydrocephalus. We present the case to highlight the importance of early investigation for IE in patients with fever of unknown origin and shunt in situ, as rapid deterioration can occur and be fatal. We also discuss past experience reported in the literature on the role of cardiothoracic intervention. Prompt diagnosis and early cardiothoracic referral for surgery are crucial, there may only be a narrow window of opportunity for intervention before patients develop fulminant sepsis.
Non-central serous chorioretinopathy in a patient with systemic lupus erythematosus and hydroxychloroquine retinopathy
Authors: Hipolito-Fernandes Diogo , Luís Maria Elisa , Flores Rita , Anjos Rita
Published: January 2021

Subretinal fluid accumulation in a patient with systemic lupus erythematosus (SLE) may represent a diagnostic challenge. We present a case of a 43-year-old man with baseline diagnosis of SLE and hydroxychloroquine-associated maculopathy who reported progressive vision loss on the right eye, associated with corticosteroids use for an arthritic crisis. Ophthalmological examination did not reveal any acute finding. On optical coherence tomography, subretinal fluid in the perifoveal area was visible on the right eye, with corresponding enlargement of the visual field defect. An increased choroidal thickness was also visible. Fluorescein angiography revealed, on the right eye, two pinpoint areas of leakage and indocyanine green angiography signs of choroidal vascular hyperpermeability. Considering a diagnosis of a non-central central serous chorioretinopathy, corticosteroids use was interrupted, with resolution of the subretinal fluid. This case illustrates the relevance of a multimodal imaging approach to guide the diagnosis of patient with an SLE with subretinal fluid.
Variants ofSLC18A3leading to congenital myasthenic syndrome in two children with varying presentations
Authors: Lamond Allison , Buckley David , O'Dea Jennifer , Turner Lesley
Published: January 2021

This report describes the variation in presentation of two unrelated patients found to have a rare form of presynaptic congenital myasthenic syndrome. Both patients presented with hypotonia, ptosis, poor weight gain and apneic episodes. Through whole exome sequencing, our patients were found to have the same likely pathogenic biallelic variants in W315X and I200N ofSLC18A3, encoding vesicular acetylcholine transporter (VAChT). These specific variants inSLC18A3have not been previously described in the literature. We illustrate the variety in clinical presentation and course of children with mutations inSLC18A3, leading to presynaptic congenital myasthenic syndrome through VAChT deficiency.
Mucin-filled CBD, difficult to manage cholangitis
Authors: Kumar Manish , Sonika Ujjwal , Sachdeva Sanjeev , Dalal Ashok
Published: January 2021

Intraductal papillary mucinous neoplasms (IPMNs) are mucin-secreting cystic neoplasm of pancreas. They have a malignant potential. They are usually localised to the pancreas but occasionally can involve surrounding structures (1.9%–6.6%), like bile duct and duodenum, and are labelled as IPMN with invasion. Jaundice as a manifestation of IPMN is not common (4.5%). It can present as jaundice as a result of invasion of common bile duct (CBD) resulting in stricture formation or uncommonly as a result of fistulising to CBD with resultant obstruction of CBD by thick mucin secreted by this tumour. As only few cases (around 23) of mucin-filled CBD are reported in the literature. We are presenting our experience in dealing a rare case of obstructive jaundice caused by IPMN fistulising into CBD, highlighting the difficulties faced in managing such case, especially with regards to biliary drainage and what can be the optimum management in such cases.
Retrieval of foreign body from maxillary sinus through extraction socket
Authors: Dadhich Anuj , Saluja Harish , Shah Seemit , Nilesh Kumar
Published: January 2021

Dry socket or alveolar osteitis is one of the most common complication following tooth extraction. Patients usually reports of pain, which typically starts on third or fourth postoperative day and responds to simple irrigation and placement of zinc oxide eugenol (ZOE) pack, which provides an obtundent effect. The pack should be loosely kept in the extraction socket and should be changed periodically to allow healing. This report presents a case of retrieval of foreign body, which actually was a ZOE pack from maxillary sinus, 6 months after the patient underwent extraction of upper left maxillary first molar.
Management of recurrent post-traumatic seroma of thigh (Morel-Lavallée lesion) by percutaneous aspiration and sclerotherapy using tetracyclines (PAST)
Authors: Gupta Arunesh , Kumar Vineet , Agarwal Apurva , Suresh Aneesh
Published: January 2021

Morel-Lavallée lesion is a chronic, recurrent collection of serous fluid in the soft tissues and usually occurs following injury. The most common sites are thigh, hip and pelvic region. This presents as a local or diffuse swelling and may cause discomfort to the patient besides being a potential site for bacterial contamination. So, early diagnosis and timely management is crucial for an early and successful outcome. The investigation modality of choice for diagnosis of these lesions is MRI. Definitive management ranges from percutaneous aspiration with or without sclerotherapy to open debridement and irrigation. Although recurrences are common with conservative management, it can be minimised with judicious use of sclerotherapy.
Radiation-induced intracranial osteosarcoma of the anterior skull base after treatment of esthesioneuroblastoma
Authors: Kappel Ari D , Bernstock Joshua D , Ditoro Daniel Francis , Lu Yi
Published: January 2021

Esthesioneuroblastoma (ENB) is an uncommon sinonasal cancer of the olfactory neuroepithelium that is typically treated with surgical resection followed by radiation therapy. Radiation-induced intracranial osteosarcoma of the skull base is a rare but devastating long-term complication of radiation therapy in this region. Here, we present a case of an 82-year-old patient who developed radiation-induced osteosarcoma of the anterior skull base and paranasal sinuses 10 years after radiation therapy following resection of an ENB. Older patients may be at risk of developing this complication earlier and with a worse prognosis relative to younger patients. Treating physicians/surgeons should be aware of this devastating complication. Patients who are treated with high-dose radiation therapy in this region should be followed for many years.
Optic pathways and brainstem involvement in posterior reversible encephalopathy syndrome
Authors: Rodrigues Sofia Grenho , Saraiva Paulo , Marques Inês Brás
Published: January 2021

Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome manifesting with acute focal signs, and concomitant neuroimaging findings of vasogenic oedema. It affects the parieto-occipital regions in a vast majority of cases, although atypical variants have been described comprising the brainstem, basal ganglia or spinal cord. We report the case of a 41-year-old woman, admitted for persistent headache and inferior altitudinal field defect in the right eye. She presented with severe, non-medicated, hypertension. Brain MRI showed findings compatible with atypical PRES, involving the brainstem and optic pathways. With antihypertensive therapy the headache remitted, although visual field remained and was interpreted in the context of a vascular aetiology—non-arteritic anterior ischaemic optic neuropathy. MRI was repeated 3 weeks later and showed almost complete reversal of the previous changes.
Fibromatosis colli leading to positional plagiocephaly with gross anatomical and sonographic correlation
Authors: Rousslang Lee K , Rooks Elizabeth A , Smith Adam C , Wood Jonathan R
Published: January 2021

Fibromatosis colli, also known as ‘sternocleidomastoid tumour of infancy’ or ‘pseudotumour of infancy’, is a rare condition involving fibrosis and swelling, or ‘tumour’ of the sternocleidomastoid muscle in newborns that typically occurs after a traumatic delivery. Although usually self-limited, fibromatosis colli can lead to congenital muscular torticollis and positional plagiocephaly due to uneven forces on the neonatal skull. Ultrasound is the diagnostic imaging modality of choice and can prevent additional imaging and unnecessary intervention.
Clostridioides difficile-induced diarrhoea following dasatinib therapy
Authors: Datta Amlan Kusum , Debnath Partha , Chakraborty Uddalak , Chandra Atanu
Published: January 2021

Dasatinib, an oral tyrosine kinase inhibitor, is approved for therapy of chronic myeloid leukaemia (CML). Common adverse effects of this therapy include myelosuppression, fluid retention and diarrhoea. However,Clostridioides difficileinfections (CDIs) in the context of dasatinib therapy, without a history of antecedent antibiotic use, has not been reported previously. We present here a case of a 36-year-old man diagnosed with accelerated phase of CML, who was started on treatment with dasatinib. Two months into therapy, he experienced profuse diarrhoea and abdominal pain. Colonoscopy revealed multiple confluent colonic mucosal ulcerations. Immunoassay study of stool revealed positiveC. difficiletoxin. The patient was started on oral metronidazole, with discontinuation of all other drugs, including dasatinib. He made a complete uneventful recovery following 2 weeks of antibiotic therapy. Chemotherapeutic agents, such as dasatinib, should be considered as possible etiological agents in the pathogenesis of CDI, even in absence of antibiotic use.
Duplicate inferior vena cava complicating the evaluation of primary aldosteronism
Authors: Spurzem Graham J , Taddonio Michael A , Rubenzik Tamara T , Bouvet Michael
Published: January 2021

A 64-year-old man with a known duplicate inferior vena cava (D-IVC) and resistant hypertension presented to our emergency department in a hypertensive crisis. He had a longstanding history of hypertension and unexplained hypokalemia treated with oral potassium supplementation. The patient was diagnosed with primary aldosteronism and MRI of the abdomen revealed a left-sided adrenal adenoma. Adrenal venous sampling (AVS) lateralised aldosterone hypersecretion to the left adrenal gland. The patient subsequently underwent an uncomplicated laparoscopic left adrenalectomy. The patient’s postoperative course was uneventful, and he was discharged on a single antihypertensive medication on postoperative day 1. D-IVC is one of several rare IVC anatomical variants that have been well described in the literature. Knowledge of this patient’s unique abdominal venous anatomy enabled successful AVS and appropriate surgical management. It is necessary to identify potential anatomical variants of abdominal venous anatomy that may complicate these invasive procedures.
Association between hemoglobin A1c variability and hypoglycemia-related hospitalizations in veterans with diabetes mellitus
Authors: Zhao Molly J Y , Prentice Julia C , Mohr David C , Conlin Paul R
Published: January 2021

Introduction

To study the impact of hemoglobin A1c (A1c) variability on the risk of hypoglycemia-related hospitalization (HRH) in veterans with diabetes mellitus.

Research design and methods

342 059 veterans with diabetes aged 65 years or older were identified for a retrospective cohort study. All participants had a 3-year baseline period from January 1, 2005 to December 31, 2016, during which they had at least four A1c tests. A1c variability measures included coefficient of variation (A1c CV), A1c SD, and adjusted A1c SD. HRH was identified during a 2-year follow-up period from Medicare and the Veterans Health Administration through validated algorithms of International Classification of Diseases (ICD)-9 and ICD-10 codes. Logistic regression modeling was used to evaluate the relationship between A1c variability and HRH risk while controlling for relevant clinical covariates.

Results

2871 patients had one or more HRH in the 2-year follow-up period. HRH risk increased with greater A1c variability, and this was consistent across A1c CV, A1c SD, and adjusted A1c SD. Average A1c levels were also independently associated with HRH, with levels <7.0% (53 mmol/mol) having lower risk and >9% (75 mmol/mol) with greater risk. The relationships between A1c variability remained significant after controlling for average A1c levels and prior HRH during the baseline period.

Conclusion

Increasing A1c variability and elevated A1c levels are associated with a greater risk of HRH in older adults with diabetes. Clinicians should consider A1c variability when assessing patients for risk of severe hypoglycemia.
Outcome of patients with prior coronary bypass surgery admitted with an acute coronary syndrome
Authors: Marcuschamer Ilan , Zusman Oren , Iakobishvili Z , Assali Abid R , Vaknin-Assa Hanah , Goldenberg Ilan , Cohen Tal , Shlomo Nir , Kornowski Ran , Eisen Alon
Published: January 2021

Background

Patients with prior coronary artery bypass graft surgery (CABG) are at increased risk for recurrent cardiovascular ischaemic events. Advances in management have improved prognosis of patients with acute coronary syndrome (ACS), yet it is not known whether similar trends exist in patients with prior CABG.

Aim

Examine temporal trends in the prevalence, treatment and clinical outcomes of patients with prior CABG admitted with ACS.

Methods

Time-dependent analysis of patients with or without prior CABG admitted with an ACS who enrolled in the ACS Israeli Surveys between 2000 and 2016. Surveys were divided into early (2000–2008) and late (2010–2016) time periods. Outcomes included 30 days major adverse cardiac events (30d MACE) (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularisation) and 1-year mortality.

Results

Among 15 152 patients with ACS, 1506 (9.9%) had a prior CABG. Patients with prior CABG were older (69 vs 63 years), had more comorbidities and presented more with non-ST elevation-ACS (82% vs 51%). Between time periods, utilisation of antiplatelets, statins and percutaneous interventions significantly increased in both groups (p<0.001 for each). The rate of 30d MACE decreased in patients with (19.1%–12.4%, p=0.001) and without (17.4%–9.5%, p<0.001) prior CABG. However, 1-year mortality decreased only in patients without prior CABG (10.5% vs 7.4%, p<0.001) and remained unchanged in patients with prior CABG. Results were consistent after propensity matching.

Conclusions

Despite an improvement in the management and prognosis of patients with ACS in the last decade, the rate of 1-year mortality of patients with prior CABG admitted with an ACS remained unchanged.
New insights in diagnostics and therapies in syncope: a novel approach to non-cardiac syncope
Authors: Brignole Michele , Rivasi Giulia
Published: January 2021

This article aims to give advice on how to identify and manage patients with syncope who are at risk of severe outcomes, that is, at risk of trauma, potentially life-threatening episodes or frequent recurrences reducing quality of life. The first step of syncope diagnostic assessment is to identify patients with cardiac syncope, and once established, these patients must receive the adequate mechanism-specific treatment. If cardiac syncope is unlikely, reflex (neurally mediated) syncope and orthostatic hypotension are the most frequent causes of transient loss of consciousness. For these presentations, efficacy of therapy is largely determined by the mechanism of syncope rather than its aetiology or clinical features. The identified mechanism of syncope should be carefully assessed and assigned either to hypotensive or bradycardic phenotype, which will determine the choice of therapy (counteracting hypotension or counteracting bradycardia). The results of recent trials indicate that ‘mechanism-specific therapy’ is highly effective in preventing recurrences. Established mechanism-specific treatment strategies include withdrawal of hypotensive drugs, applying fludrocortisone and midodrine for the hypotensive phenotype and cardiac pacing in the bradycardic phenotype.
Deletion of Cbl-b inhibits CD8+ T-cell exhaustion and promotes CAR T-cell function
Authors: Kumar Jitendra , Kumar Ritesh , Kumar Singh Amir , Tsakem Elviche L , Kathania Mahesh , Riese Matthew J , Theiss Arianne L , Davila Marco L , Venuprasad K
Published: January 2021

Background

Chimeric antigen receptor (CAR) T-cell therapy is an emerging option for cancer treatment, but its efficacy is limited, especially in solid tumors. This is partly because the CAR T cells become dysfunctional and exhausted in the tumor microenvironment. However, the key pathways responsible for impaired function of exhausted cells remain unclear, which is essential to overcome CAR T-cell exhaustion.

Methods

Analysis of RNA-sequencing data from CD8+ tumor-infiltrating lymphocytes (TILs) led to identification of Cbl-b as a potential target. The sequencing data were validated using a syngeneic MC38 colon cancer model. To analyze the in vivo role of Cbl-b in T-cell exhaustion, tumor growth, % PD1+Tim3+ cells, and expression of effector cytokines were analyzed in cbl-b+/+ and cbl-b–/– mice. To evaluate the therapeutic potential of Cbl-b depletion, we generated a new CAR construct, hCEAscFv-CD28-CD3ζ.GFP, that recognizes human carcinoembryonic antigen (CEA). cbl-b+/+ and cbl-b–/– CEA-CAR T cells were generated by retroviral transduction. Rag–/– mice bearing MC38-CEA cells were injected with cbl-b+/+ and cbl-b–/–; CEA-CAR T cells, tumor growth, % PD1+Tim3+ cells and expression of effector cytokines were analyzed.

Results

Our results show that the E3 ubiquitin ligase Cbl-b is upregulated in exhausted (PD1+Tim3+) CD8+ TILs. CRISPR-Cas9-mediated inhibition of Cbl-b restores the effector function of exhausted CD8+ TILs. Importantly, the reduced growth of syngeneic MC38 tumors in cbl-b–/– mice was associated with a marked reduction of PD1+Tim3+ CD8+ TILs. Depletion of Cbl-b inhibited CAR T-cell exhaustion, resulting in reduced MC38-CEA tumor growth, reduced PD1+Tim3+ cells and increased expression of interferon gamma, tumor necrosis factor alpha, and increased tumor cell killing.

Conclusion

Our studies demonstrate that deficiency of Cbl-b overcomes endogenous CD8+ T-cell exhaustion, and deletion of Cbl-b in CAR T cells renders them resistant to exhaustion. Our results could facilitate the development of efficient CAR T-cell therapy for solid tumors by targeting Cbl-b.