Introduction: The second wave of coronavirus disease 2019 (COVID-19) led to the resurgence of opportunistic infections due to the injudicious use of steroids. Sinonasal mucormycosis was declared an epidemic in India during the pandemic. Mucormycosis was managed effectively by surgical debridement along with systemic amphotericin B. Currently, a resurgence of mucormycosis following initial treatment, in the form of fungal osteomyelitis of the frontal bone, is being seen in India.
Methods: This prospective study included 10 patients with fungal osteomyelitis of the frontal bone due to mucormycosis. All patients underwent surgical debridement of the sequestrum and involucrum, with systemic antifungal pharmacotherapy.
Results: The average duration of time until mucormycosis recurrence was 22 days following initial treatment (range 10–33 days). Patients presented with extracranial bossing following outer frontal cortex erosion (n=3), bicortical erosion (n=3), bifrontal involvement (n=2), dural involvement (n=3), and involvement of the brain parenchyma and prefrontal cortex (n=2). All cases underwent debridement of the entire sequestrous bone and involucrum until normal bone could be identified. The mean admission duration was 4 weeks (range 3–6 weeks). All treated patients are currently alive and without disease, confirmed by contrast-enhanced computed tomography.
Conclusion: Based on our experience, the successful treatment of fungal osteomyelitis due to mucormycosis requires a four-pronged approach: early detection, multidisciplinary management of comorbidities, surgical debridement of necrotic bone, and adequate systemic antifungal therapy.
The Joles Jewish Hospital in Haarlem (a small city in the Netherlands) was established in 1930 to provide a Jewish milieu for local patients. Mozes Joles, a wealthy Jewish businessman, bequeathed his fortune to the Haarlem Jewish community to accomplish this objective, and its spiritual leader, Rabbi Simon Philip de Vries, was the driving force in successfully achieving this goal. The Joles Hospital was forcibly closed by the Nazis in 1943, and the postwar leadership of the Haarlem Jewish community decided not to reopen it. Instead, they used the Joles inheritance to build old age homes in both Haifa, Israel, and Haarlem, thus ensuring a Jewish environment for elderly care in both locales. The realization of one man’s charitable act bettered the lives of both ill and elderly individuals.
The aftermath of the Second World War and the Holocaust triggered mass migration of Jewish refugees to British Mandatory Palestine and, after 1948, the nascent State of Israel. Responding to this crisis, Jews in the Diaspora increased their commitment to facilitate immigration to Israel, particularly by supporting medical services to the Yishuv (pre-state Jewish Settlement). This paper explores the critical role played by Hadassah and other organizations in establishing direct medical services for Jewish immigrants during two key periods of Israel’s history: the end of British Mandatory Palestine (1944–1948) and the early years of the State of Israel (1948–1953). While the Immigrant Medical Services organization faced numerous challenges, this organization was essential in addressing the pressing healthcare needs of a burgeoning population amid morbidity and mortality concerns. An emphasis is placed on the challenges faced by these organizations and the commitment and resourcefulness of all involved, which ultimately shaped the foundation of Israel’s healthcare infrastructure.
Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.
Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained vir-al response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, pro-longed, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fi-brinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to pre-dict disease progression in HCV patients and be a logical target for the development of novel therapeu-tic approaches for the treatment of patients with HCV infection.
The closest living relatives of humans are their chimpanzee/bonobo (Pan) sister species, members of the same subfamily “Homininae”. This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psy-chology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabili-ties, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, fa-cial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human–chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Austra-lopithecus, need to be included in Australopithecine‟s subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cul-tural evolutionary origins.
This paper describes the rapid evolution of modern liver surgery, starting in the middle of the twentieth century. Claude Couinaud studied and described the segmental anatomy of the liver, Thomas Starzl performed the first liver transplantations, and Henri Bismuth introduced the concept of anatomical resections. Hepatic surgery has developed significantly since those early days. To date, innovative techniques are applied, using cutting-edge technologies: Intraoperative ultrasound, techniques of vascular exclusion of the liver, new devices for performing homeostasis and dissection, laparoscopy for resections, and new drugs that allow the resection of previously unresectable tumors. The next stage in liver surgery will probably be the implementation of a multidisciplinary holistic approach to the liver-diseased patient that will ensure the best and most efficient treatments in the future.
High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler.
Research over the past 10 years in our laboratory has led to two major findings. The first is that haptoglobin (Hp) genotype can predict the risk of developing vascular complications in individuals with diabetes mellitus (DM), and the second, more far-reaching discovery, is that vitamin E treatment can significantly reduce vascular complications in individuals with DM and the Hp 2-2 genotype. The former finding has been well documented in numerous studies which included over 50,000 patients of diverse geographical and ethnic backgrounds. The latter discovery is more recent and less well accepted by the medical community due to confounding reports over the past 30 years regarding the efficacy of vitamin E treatment for vascular disease. We propose that the benefit of vitamin E treatment was not obvious in earlier studies due to the absence of any genetic basis for patient selection. Our studies dividing DM individuals into vitamin E treatment subgroups based on Hp genotype show a clear benefit for individuals of the Hp 2-2 genotype, while patients carrying the other two Hp genotypes are not affected or may be adversely affected by receiving vitamin E. These findings may explain the overall lack of benefit seen in previous vitamin E studies and emphasize the importance of carefully selecting which patients should receive vitamin E therapy. The pharmacogenomic paradigm discussed in this review potentially could result in a dramatic improvement in the health of millions of individuals worldwide using a treatment that is both accessible and affordable to all.
In this brief review, written from the perspective of a physician-leader who has fostered the development of comprehensive quality improvement efforts at two academic medical centers, I review the need for improvement, some conceptual barriers that must be overcome, the goals of a comprehensive quality improvement (QI) effort, some of the results we have obtained, and some observations on how to develop a culture of continuous improvement in an academic medical center. The mandate for quality improvement is clear; current healthcare is wasteful and error-prone, leading to excessive morbidity and mortality and unsustainably high costs. Successful quality improvement requires the abandonment of two paradigms: the craft model of medical practice and the notion that many forms of harm to patients are not preventable. I will describe how dramatic improvement has been achieved in reducing, by up to 10-fold, rates of central line infections, ventilator-associated pneumonias, peritonitis in peritoneal dialysis patients, and mortality due to cardiac arrest in hospital. I will describe as well how these methods can improve access to out-patient clinics dramatically and enhance the reliability and safety of hand-offs between covering physicians. To develop and maintain systematic quality improvement in all phases of medical care we must articulate a culture in which: everyone working at the medical center makes improvements every day; front-line staff, who know best how the work is done, are empowered to improve the processes of care; and multidisciplinary teams create the protocols that reduce variation that is due to physician preference, leaving only the variation required by the individual needs of patients. I will review as well the crucial elements of education of trainees and faculty members needed to guide and sustain a culture of quality. Finally, I will add some observations on how oversight boards and medical center leaders can help create systematic quality improvement in their medical centers.
