Esophageal atresia is a congenital malformation incompatible with life due to the inability to eat on the one hand but also to tracheobronchial flooding.

We read with interest the article by Perez-Cruz et al. [1] about a 46 years old male with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome [1]. Initially, immune encephalitis was suspected why the patient underwent brain biopsy and received steroids without benefit (Pérez-Cruz, E. et al., 2022). Work-up for MELAS revealed basal ganglia calcification, two stroke-like lesions in a right temporal and the left temporo-occipital distribution, lactic acidosis in the serum and cerebrospinal fluid (CSF) and the mtDNA variant m.3243A>G in MT-TL1 [1]. Immuno-nutrition, a so called mitochondrial cocktail, together with anti-seizure drugs (ASDs) was initiated, this time with a beneficial effect [1]. The study is appealing but raises concerns that need to be discussed.
 

It is not comprehensible why initially immune encephalitis was suspected and why work-up for it was initiated and why the patient received ex juvantibus steroids [1]. The patient was of short stature, had a previous history of diabetes, hearing impairment, tinnitus, partial complex seizures (left leg, visual hallucinations, unconsciousness, secessus), quadruparesis and had elevated lactate in the serum and the cerebrospinal fluid (CSF) on admission [1]. Additionally, cerebral CT revealed bilateral basal ganglia calcification, which is a typical feature of mitochondrial disorders on cerebral imaging [2]. Furthermore, echocardiography revealed systolic dysfunction, frequently observed in patients with a mitochondrial disorder and cardiac involvement [3]. Patients with immune encephalitis usually do not develop lactic acidosis in the serum or CSF unless they experience seizures. We should know why nonetheless immune encephalitis was suspected and why brain biopsy had been carried out and why steroids were given. Steroids can be harmful to patients with a mitochondrial disorder, particularly in patients with Kearns-Sayre syndrome [4]. Application of steroids is particularly critical in diabetic patients. Brain biopsy is an invasive diagnostic measure with a high risk of complications, such as infection, bleeding or seizures.
 

Missing is the heteroplasmy rate of the m.3243A>G variant and the tissue in which heteroplasmy was determined. Knowing heteroplasmy rates in various different tissues is crucial for assessing the phenotypic spectrum, progression and outcome of MELAS patients and for genetic counselling.
 

Missing is the information if the variant m.3243A>G was inherited from the mother of if it occurred spontaneously. Since three quarters of the MELAS patients inherit the culprit mutation from their mothers [5], it is essential to know if the index patient’s mother was clinically affected or if she carried the m.3243A>G variant as well. Furthermore, we should know if other first degree relatives were clinically affected or carried the culprit variant as well.
 

MELAS should not be diagnosed upon the Hirano criteria [6], which stem form 1992 and require the triad of encephalopathy, lactic acidosis and stroke-like episodes (SLEs) but rather according to the Japanese criteria [7]. The Japanese criteria have been published in 2012 and require the presence of more subtle phenotypic features and the presence of a causative mutation.
 

There is a discrepancy between the history of hearing loss and tinnitus two months prior to admission and the normal status of cranial nerves on clinical neurologic exam. We should be told if the patient was hearing normally or not on admission.
 

MELAS is associated with permanent or episodic lactic acidosis in the majority of the cases [8]. We should be told why the patient nonetheless received metformin during 7 months since evolvement of diabetes prior to admission. Missing is the HbA1c value.
 

The authors described a hyperintense lesion on fluid attenuated inversion recovery (FLAIR) in the “cerebellar lobe” [1]. We should be told if it was the right or left lobe and if this lesion was also hyperintense on Diffusion-Weighted Imaging (DWI). Is it conceivable that this lesion met the criteria for being classified as a SLL?
 

Though nutritional and lifestyle modifications may have a temporary beneficial effect on the disease course [9], MELAS is usually a progressive disease from which patients die prematurely. From none of the compounds usually administered to MELAS patients is a long-term benefit documented by prospective studies with a double blind placebo-controlled design. L-carnitine will be beneficial only in case of confirmed carnitine deficiency. Since mitochondrial disorders, including MELAS, are highly sensitive to drugs, compounds with a mitochondrion- toxic effect should be avoided. This is particularly the case for certain ASDs, such as phenytoin, carbamazepin, valproic acid and barbituric acid [9].
 

Though the patient underwent muscle biopsy, no results of this investigation were presented [1]. We should be told if any morphological abnormalities of the mitochondria were found, if immune histochemistry revealed COX-deficient fibers or if there were SDH hyper-reactive fibers. Were ragged-red fibers detected upon the Gomori stain? It would be also interesting to know if the variant m.3243A>G was detected in muscle and if the heteroplasmy rate was higher as compared with other tissues.
 

Overall, the interesting study has several limitations which challenge the results and their interpretation. Addressing these issues would strengthen the conclusions and could be more educative. Patients with a mitochondrial disorder should not receive mitochondrion-toxic drugs. Patients in whom a mitochondrial disorder is suspected should not undergo brain biopsy. Treatment of MELAS currently remains symptomatic and supportive.

Ethical Approval
Ethical approval was in accordance with ethical guidelines. The study was approved by the institutional review board.

Epilepsy associated with slow growing brain tumors may frequently be the cause for pharmacoresistant focal seizures in young children. Dysembryoplastic neuroepithelial tumor is one such entity which may cause epilepsy resistant to multiple antiepileptic agents. Focal cortical dysplasia, a congenital cortical developmental anomaly which may be seen associated with DNET, independently acts as an epileptogenic focus. Early diagnosis of such lesions is necessary. Long term use of antiepileptic drugs (AEDs), needed for control of tumor related epilepsy and might affect the cognitive development of the child. Complete surgical removal of the tumor along with overlying dysplasia is one of the modalities for making the patient seizure free. However, the risks of surgery and neurological development post-surgery should also be considered while deciding on the management of LEATs in pediatric patients.

Background: Present study was done to evaluate the Socio-demographic characteristics, Classifications and Clinical Parameters among patients of proximal tibial fractures treated with open reduction internal fixation with locking compression plate. Material and Methods: The study was conducted during 1^st August 2019 to 31^st October 2020 in the Department of Orthopaedic Surgery, Indira Gandhi Medical College Shimla that included 21 prospective and 4 retrospective cases who fulfilled the inclusion criteria with closed tibial plateau fracture. Results: All the patients were above 18 years of age; 60% of patients were between 31 to 60 years with mean age of 42.5±14.4 years. There were 21 males and 4 females. The ratio between male to female patients was 5.3:1. Most of the patients were farmers and private job workers by occupation. Involvement of left extremity was more common (68%) than right. Mode of injury was fall in 72% and road side accident in 28% of the patients. According to Schatzker classification-type II (48%) and type V (24%) were most common type. Partial articular (41B3) and 41C3 (complete articular) were the most common AO/OTA type. Majority (44%) of the patient had single column involvement according to Sun and Luo classification. Sixteen percent of the patients had associated skeletal injuries. Most of the patients were operated within 7 days of injury. The average duration between injury and surgery was 4.68±5.4 days. Sixty six percent of the patients were discharged within 7 days after surgery. The mean duration of stay after surgery was 10.7±11.5 days. All the fractures were united in our study with average union time of 14.2±1.4 weeks. Conclusion:Majority of patients were young and in active age group young, males, farmers or private job workers by occupation, had Involvement of left extremity, had fall as a Mode of injury, had associated skeletal injuries, operated within 7 days of injury and were discharged within 7 days after surgery.

Background: The present study was done to evaluate the Association between Various socio-demographic and clinical Parameters with Functional Scores after open reduction and internal fixation of acetabulum fractures. Material and Methods: The present study was done in 44 patients of fracture acetabulum managed by open reduction internal fixation in the Department of Orthopaedic surgery, Indira Gandhi Medical College, Shimla. The functional and radiological outcome was assessed by Modified Merle d’Augbigne Postel score, Modified Harris Hip score and radiological scoring by Matta et al., at every follow up in prospective patients and at last follow up in retrospective patients. Results: There were 16 prospective (36.4%) and 28 retrospective (63.6%) cases. Incidence more in younger age group (21-60 years). There was Male predominance and more patients had rural background. RSA was the most common mode of injury in 63%. Autogenous bone graft from/Illiac Crest/ Greater trochanter was used for posterior wall impaction/ reconstruction. Mean Blood loss was more in anterior approach than posterior. Simple fractures had lesser mean hospital stay. Simple fractures were more common and had significantly better functional outcome than associated fracture types. Functional outcome was significantly better when operated within 2 weeks. Functional Outcome of Anterior approach was significantly better than posterior because of fewer complications. Functional Outcome was significantly better in patients with anatomical reduction. Modified Merle d’Aubigne and postel (MDA) score was excellent in 77%patients, good in 13%, fair in 10%. Matta’s radiological score at final follow up was excellent in 54.55%, good in 36.36%, fair in 4.55% and poor in 4.54% patients.The average Modified Harris Hip score was excellent in 97% and fair in 3% of patients. Complications were seen in only 2(4.45%) patients. Conclusion: Study concluded that those having Simple fractures, operated within 2 weeks, anterior surgical approach with anatomical reduction had significantly better functional outcome because of less complications.

Acute megakaryoblastic leukemia is a very rare entity of Acute Myeloid Leukemia (AML), usually with a severe prognosis. It is extremely rare in adults, occurring in only 1% of AML patients. This is in contrast to children, where it included between 4 and 15% of AML patients. Its diagnosis calls for a multidisciplinary approach. Based primarily on the presence in the blood or in the bone marrow of blasts with a typical morphology of the megakaryocytic line. This is superseded by immunophenotyping for blasts expressing specific platelet antigens. The epidemiological, clinical, cytological and immunophenotypic aspects of acute megakaryoblastic leukemia (AMegL) are described through this observation of a 2-year-old kid who presented with bone marrow failure syndrome and bi-cytopenia.

Systemic amyloidosis is deposition of amyloid in multiple organs with characteristic  histopathologic findings including apple –green birefringence with Congo red staining on polarized light microscopy. We report a case of systemic amyloidosis in 60-year-old man with abdominal distension, weight loss and fatigue. The diagnosis of amyloidosis was done by abdominal fat pad biopsy. At the 3-months follow up, the patient referred to hematologist who advised the patient to do bone marrow biopsy. The patient’s clinical condition had not changed. Conclusion: Further work up and investigations are required to diagnose amyloidosis in patient presented with hepatomegaly, weight loss, nephrotic syndrome, bleeding tendency, peripheral neuropathy and cardiomyopathy.

We eagerly read the article by Santos et al [1] about a retrospective study of the risk factors for delirium in a cohort of 162 American veterans hospitalised for a SARS-CoV-2 infection between March 1 2020 and April 20 2020 [1]. It was found that length of hospitalisation and newly diagnosed cardiac disease were the only factors increasing the odds for delirium in a logistic regression [1]. The study is appealing but raises concerns which require discussion. 

The main limitation of the study is its retrospective design implicating that work up for delirium in each individual patient may have focused on different aspects and investigations with variable results but no results of a defined battery of prospective investigations.

A further limitation is that results of cerebral imaging (cerebral computed tomography (CCT), cerebral magnetic resonance imaging (cMRI)), of electroencephalography (EEG) recordings, and cerebro-spinal fluid (CSF) investigation were not included in the study. Several manifestations of neuro-COVID may go along with delirium. These include autoimmune encephalitis, venous sinus thrombosis [2], meningitis [3], ischemic stroke [4], and intra-cerebral bleeding. 

In a retrospective study of 32 patients with SARS-CoV-2 associated meningitis/encephalitis, 19% of the patients manifested with delirium [3]. In a study of 1017 patients with COVID-19 pneumonia, 16% developed a delirium. Interestingly, 79% of these patients were under mechanical ventilation when delirium was diagnosed. Twenty-three percent of those with a delirium died. Against that, there was no association between respiratory failure and delirium in the index study [1]. 

Missing are data about how many of the included patients were alcoholics or drug-dependent and developed delirium in the context of a withdrawal syndrome. Missing is the information about the current medication the included patients were taking until admission. Several drugs, particularly benzodiazepines or antidepressants may be associated with delirium in case of immediate discontinuation.

Missing is the information about the severity of COVID-19 infection in the 162 included patients [1]. Generally, there is an increased risk of developing delirium among COVID-19 patients requiring mechanical ventilation, patients requiring extra-corporal membrane oxygenation (ECMO), and patients with sepsis, immune thrombocytopenia, or hypercoagulability syndrome. 

Missing is the information about the drugs the included patients newly received during hospitalisation. One of the drugs frequently applied for the treatment of COVID-19 is the interleukin (IL)-6 inhibitor tocilizumab. A 70yo male with COVID-pneumonia who was treated off-label with tocilizumab developed a prolonged delirium. Favipiravir has been reported to cause malignant neuroleptic syndrome in some COVID-19 patients which may be associated with delirium. Another drug frequently applied for the treatment of COVID-19 is chloroquine. In a retrospective evaluation of data from the FDA Adverse Event Reporting System (FAERS) database, 520 patients were identified who developed neuropsychiatric adverse events following the use of chloroquine. Using a multilevel model, exposure to chloroquine was associated with high reporting of delirium, amnesia, hallucinations, depression, and loss of consciousness. 

Overall, the study has limitations which challenge the results and their interpretation. These limitations should be met to strengthen the conclusions. The number of risk factors for developing delirium during COVUD-19 is higher than presented. 

Declarations

• The authors declare no conflicts of interest

• No funding was received

Author contribution

• JF: design, literature search, discussion, first draft, critical comments

• Informed consent: was obtained

• The study was approved by the institutional review board

We eagerly read the article by Valdes et al. [1] about the cognitive deficits among 215 patients 6 months after a SARS-CoV-2 infection requiring hospitalisation as assessed by the tMoCA test via telephone [1]. It was found that fewer years of education, black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6 months post-hospitalization for COVID-19 [1]. The study is appealing but raises concerns which require discussion. 

Cognitive dysfunction as a feature of post-COVID syndrome at 6 months after the infection will not only depend on the demographics and social determinants of health (SDOH) but also on the type and degree of CNS involvement (neuro-COVID) and the drugs given during or after the acute infection. Thus, cognitive dysfunction cannot be reliably assessed without knowing type and degree of neuro-COVID as assessed by clinical, blood chemical, cerebral imaging and Cerebro-Spinal Fluid (CSF) investigations. Type and extension of structural lesions on cerebral imaging need to be included in the evaluation as most of the cerebral manifestations of neuro-COVID go along with cognitive dysfunction [2]. Accordingly neuro-COVID manifestations such as ischemic stroke, cerebral bleeding, Acute Hemorrhaghic, Necrotising Encephalitis (AHNE), multifocal Posterior Reversible Encephalopathy Syndrome (PRES), Acute, Disseminated Encephalomyelitis (ADEM), Venous Sinus Thrombosis (VST), Reversible, Cerebral Vasoconstriction Syndrome (RCVS), meningitis, encephalitis, neuromyelitis optica, cerebral vasculitis and cerebral hypoxia need to be appropriately excluded by cerebral imaging as a possible cause of cognitive impairment following a SARS-CoV-2 infection.

Missing in the study is the status of SARS-CoV-2 vaccinations. Since SARS-CoV-2 vaccinations are potentially neurotoxic [3] and can be complicated by a myriad of CNS complications, it is crucial to include the vaccination status of each included patient in the evaluation. The most common neurological complications of SARS-CoV-2 vacciantions affecting the CNS include headache, VST, immune encephalitis, multiple sclerosis, neuromyelitis  optica,  stroke,  cerebral  bleeding  and ADEM [3]. 

To reliably asses the influence of SARS-CoV-2 infections on cognitive functions it would be appropriate to investigate COVID-19 patients already during the infection and several times after the acute stage of the infec6tion. Exploration of a COVID-19 patient only once will miss the dynamics and fluctuations of cognitive impairment and thus the influence of co-factors.

Another limitation of the study is that it was carried out by telephone interviews. Disadvantages of telephone interviews are that the identity of the patient remains unconfirmed, that no clinical neurologic exam can or on-site psychiatric exploration can be carried out and that the responsiveness to questions and tasks of a psychological tests will differ between an anonymous remote setting compared with face-to-face interactions.

A further limitation is that the current medication was not included in the assessment of cognitive dysfunction. From several drugs it is known that they can significantly influence cognitive functions (e.g., benzodiazepines, neuroleptics, serotonin-reuptake inhibitors).

Overall, the study has limitations which challenge the results and their interpretation. These limitations should be addressed to strengthen the conclusions. Causality of cognitive dysfunction following a SARS-CoV-2 infection is more widespread than anticipated.

Background: Acute pancreatitis is a common clinical entity, common causes being chronic alcohol consumption and gallstones. Acute episode of pancreatitis is uncommonly reported with a case of primary hyperparathyroidism. So, here we present a 33-year-old male who presented with acute abdomen caused by acute pancreatitis with no history of gallstones and alcohol consumption. He was further investigated for other uncommon causes of pancreatitis and found to have hyperparathyroidism caused by parathyroid adenoma. Hence, we suspect hypercalcemia induced by parathyroid adenoma can be a causative factor for the acute pancreatitis patients. Case Summary: We are reporting a case of 33-year-old male who presented with chief complaint of severe pain in epigastric region associated with vomiting and mild abdominal distension. With clinical, biochemical and image modalities a confirmed diagnosis of acute pancreatitis was made. On detailed investigations he was found to have hypercalcemia and increased parathyroid hormone levels. Patient was managed conservatively initially but due to repeated episodes of pain abdomen and persistent severe hypercalcemia with significant ECG changes showing bradycardia and prolonged QT interval, parathyroid adenoma was excised and renal stones were removed. After parathyroid excision patient improved drastically and parathyroid hormone levels came to a normal range post-operatively but hypocalcemia was seen post operatively which was medically managed successfully. Conclusion: Acute pancreatitis is a uncommon first clinical manifestation of hyperparathyroidism induced hypercalcemia.

Motor neuron disease (MNDs) is a neurodegenerative illness with unknown cause, often called amyotrophic lateral sclerosis (ALS). To put it another way, respiratory failure is the most common cause of mortality from progressive muscular weakening and bulbar dysfunction. Until all of the clinical signs and symptoms are present, it may be difficult to confirm the diagnosis [1]. All types of the illness have a considerable differential diagnosis to consider, including curable disorders, thus a professional neurology opinion should always be obtained. Even while only a small percentage of individuals with familial ALS can be shown to have a clear genetic inheritance, research into the biochemical basis of genetic subtypes is yielding crucial results that might one day lead to therapies for sporadic cases of the illness [2]. When there is no cure or disease-modifying treatment, care is supportive and involves a multidisciplinary team. Complex hereditary and environmental variables may play a role in the development of motor neuron disease, and future therapy may include a mix of molecular medicines or stem cell transplants to restore cell integrity. Patients with MND or ALS suffer from a gradual degenerative illness that has no recognized cause. It is helpful to think about the diverse manifestations of motor neuron illnesses in terms of the relative involvement of upper and lower motor neurons when considering the differential diagnosis.

Introduction: Schwannoma is a tumor of nerve origin that develops at the expense of Schwann sheath cells. It has a ubiquitous distribution in the body. Located in the digestive tract, together with leiomyomas, leiomyosarcomas and leiomyoblastomas, it constitutes the group of GISTs. The rarity and risk of malignant transformation of this condition prompted us to report a case observed at the University Hospital Center of Libreville. Observation: EOS, 58 years old, with a history of bilateral ovarian cystectomies, had consulted for cessation of gas matter, with bloating and abdominal pain. Clinical examination revealed an occlusive syndrome without a palpable mass. The ASP had revealed hailstorm-like hydro-aeric levels. Surgical exploration revealed a large solid obstructive ileal mass located 50 cm from the ileocecal junction with dilation of the loops upstream. A segmental carcinological resection with anastomosis in one step was performed. Histological analysis of the specimen revealed a low-grade malignant schwannoma with positive PS 100 antibody. The post-operative course was straightforward. The patient was discharged on D10 postoperative. The CT scan performed after 3 months was unremarkable. Conclusion: schwannoma is a rare condition, as is its intestinal location. The treatment is surgical. Surveillance is necessary, linked to the risk of recurrence and malignant transformation.

Most commonly encountered malignancies of esophagus are squamous and adenocarcinoma. Neuroendocrine carcinomas of esophagus are very rare, mostly are poorly differentiated carcinomas. These carcinomas are aggressive and have poor prognosis. Here we present a case of 54-year-old male with chief complaint of pain abdomen. Upper GI endoscopy revealed an uleroproliferative growth in lower third of esophagus. Histopathology diagnosis was poorly differentiated neuroendocrine carcinoma. Radiological studies revealed growth in lower third of esophagus with liver metastasis.

Henoch-Schonlein Purpura is a small vessel vasculitis which affects children aged between 3-10 years. The disease is characterized by palpable purpura, bowel angina, arthralgia and renal involvement. The disease is self limiting but can cause renal failure. The case discussed was presented in the OPD with bowel symptoms and subsequently developed rash. The case was diagnosed and managed in the outpatient visits and is on follow-up for long term renal complications.

Background: Present study was done to evaluate the socio-demographic & clinical profile of patients having gall bladder perforation and spillage of bile & gall stones during laparoscopic cholecystectomy. Material & Methods: This prospective study was conducted in the Department of General Surgery, IGMC, Shimla. 100 consecutive patients of symptomatic gallstones with the documented gallstones undergoing laparoscopic cholecystectomy between July 2011 to March 2012 were included in the study and a study of gall bladder perforation and spillage of bile and gall stones was done. Results: In the present study majority of patients were females (86%) and males were only 14%. Mean age of the females was 40.15±10.97 years and in the male patients it was 47.64 years. Majority of the patients presented with symptoms of pain right upper abdomen (96%), dyspepsia (37%) and most of the patients had symptoms for a period of 1-6 months (37%). There were 16 patients with previous lower abdominal surgery.4% of the patients had multiple stones on ultrasound whereas 26% had single stone on ultrasound. 68% of the patients had gallbladder stone up to 1cm in size. The gallbladder wall thickness in 29% of patients was up to 2mm and in 48% patients was between 2.1 -3 mm. Among the total, 53 patients (53%) had distended gall bladder without any adhesions and 22 patients (22%) had distended gallbladder with adhesions with omentum. Conclusion: Majority of patients in this study were females, in age group of 31- 40 years, had pain right hypochondrium, had multiple stones with size ≤10 mm and had gallbladder thickness ranging between 2.1-3mm.